Study results promising for hepatitis C patients awaiting or completing liver transplant
AN ANTONIO (April 30 2015) -- A number of new, highly effective oral treatments for various types of hepatitis C have been approved in the past few years. However, two groups who have not benefitted from the new treatments are patients with hepatitis C who have advanced liver disease and patients who have received a liver transplant but the advanced liver disease has returned because of hepatitis C.
"The problem for these patients is that unless the hepatitis C is cured, the virus continues circulating in their blood infecting the new liver, usually within a few months of transplant. One-third of them have cirrhosis again within five years," explained Fred Poordad, M.D., clinical professor of medicine and chief of hepatology at The University of Texas Health Science Center at San Antonio.
"This puts these patients back at high risk of dying from chronic hepatitis C or liver disease," said Dr. Poordad, principal investigator of the ALLY-1 study, who presented the results April 25 at The International Liver CongressTM of the European Association for the Study of the Liver (EASL) in Vienna, Austria.
The Phase III clinical trial evaluated a 12-week course of daclatasvir - the new drug being evaluated - combined with sofosbuvir and ribavirin for patients with chronic hepatitis C. Patients accepted into the trial either had a liver transplant with returning hepatitis C or had hepatitis C with advanced cirrhosis (scarring of the liver).
Study results showed an overall cure rate of 94 percent for patients with a liver transplant and returning hepatitis C, and 83 percent for patients with advanced cirrhosis.
The study's primary endpoints also were reached, with 95 percent of post-transplant genotype 1 patients and 82 percent of genotype 1 patients with advanced cirrhosis being cured 12 weeks after treatment. Patients with other genotypes of the disease were enrolled as well, with benefits seen in all groups.
Genotypes are subgroups or strains of a disease, such as hepatitis C. There are many subtypes of hepatitis C based on the geographic regions where the strain is most prevalent. Over time, each strain evolved differently so that treatments are based on the genotype of the disease. For example, genotype 1 is the type of hepatitis C most common in the United States and is the most difficult to treat.
The study regimen was well tolerated and showed few serious side effects. "Transplant patients take a variety of medications to prevent organ rejection that can complicate the treatment of hepatitis C. In ALLY-1, we saw no drug-to-drug interactions between transplant and hepatitis C therapies and no need to make close adjustments to patients' transplant-related drugs while they received the hepatitis C regimen," Dr. Poordad said.
The ALLY-1 study was conducted at five major transplant centers in San Antonio and Houston, Texas; Miami, Fla.; Ann Arbor, Mich., and Seattle, Wash.
Hepatitis C is a liver disease found worldwide that is spread though contact with blood or semen, such as shared drug injection needles, inadequate sterilization of medical equipment, unscreened blood and blood products, accidental needle sticks in the health profession, and sexual intercourse with a person who has hepatitis C. The disease also can be passed from mothers to their children through the birthing process.
According to the U.S. Centers for Disease Control and Prevention, 3.2 million people in the U.S. have chronic hepatitis C, and 70 to 80 percent do not have symptoms. Nonetheless, it is a serious disease that can lead to long-term health problems such as liver damage, liver failure, liver cancer and death. It is often discovered later, after significant liver damage has occurred.
In the U.S., people born between 1945 and 1965 have the highest risk of hepatitis C due to higher drug use. People in this age group are urged to have a one-time blood test for hepatitis C to detect the virus and begin receiving treatment, if necessary, before significant liver damage occurs. There is no vaccine to prevent hepatitis C.
Daclatasvir, a drug developed by Bristol-Myers Squibb, was approved in Europe in 2014 for use with other medications for genotypes 1 through 4 for the treatment of chronic hepatitis C in adults. It is also approved in Japan as well as many countries in Central and South America, the Middle East and Asia Pacific. Daclatasvir regimens also have been included in the EASL's recommendations for the treatment of hepatitis C in Europe.
The U.S. Food and Drug Administration is reviewing daclatasvir for possible approval in the United States.
###
For current news from the UT Health Science Center San Antonio, please visit our news release website, like us on Facebook or follow us on Twitter.
The University of Texas Health Science Center at San Antonio, one of the country's leading health sciences universities, ranks in the top 13 percent of academic institutions receiving National Institutes of Health (NIH) funding. The university's schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced more than 29,000 graduates. The $787.7 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways "We make lives better®," visit http://www.uthscsa.edu.
Thursday, April 30, 2015
EASL 2015 Review - Internet symposium:The Advances in Chronic Hepatitis C: Management and Treatment program
CLICK HERE TO VIEW A REPLAY OF THE 4/27/15 PROGRAM
ViralEd has released a must watch Internet symposium with HCV experts discussing key data presented at this months EASL.
The Advances in Chronic Hepatitis C: Management and Treatment program is a comprehensive, expert review of the 50th Annual Meeting of the European Association for the Study of the Liver (EASL 2015). This program consists of four components: (1) CME Internet Symposium: EASL 2015 Review: a 1.5 hour Internet symposium that features an overview and discussion of key presentations and posters, selected by the expert faculty discussants; (2) CME Internet Symposium: European Perspective on EASL 2015: a 1-hour Internet symposium featuring Europe-based expert faculty reviewing and discussing key presentations with a focus on management and treatment in the EU; (3) Rapid-Fire Review of EASL 2015: a podcast that provides a brief, audio summary of the most essential data presented at the conference; and (4) From Conference To Clinic: Reviewing And Applying Data From EASL 2015: case-based dinner meetings during which the key data are reviewed, discussed and applied to patient care.
The CME Internet Symposium: EASL 2015 Review will feature four HCV experts reviewing and discussing key presentations on chronic hepatitis C presented at EASL 2015. The review and discussion will focus on HCV therapeutic options and developments, including: current treatment and management strategies, algorithms and recommendations; therapies in development; epidemiology; and diagnosis and clinical management of specific patient populations, including HCV/HIV co-infected and cirrhotic patients.
This activity will enable participating health care providers caring for HCV-infected patients to become aware of and understand the data presented at this important conference and appropriately utilize those data to improve patient care. All online components of the program can be accessed at www.viraled.com.
This program is produced by the Postgraduate Institute for Medicine and ViralEd, Inc. It is not a session created by or presented at EASL 2015 and it is not sanctioned by the organizers of EASL 2015.
The Advances in Chronic Hepatitis C: Management and Treatment program
REPLAY from 4/27/15 is Available. Join program chair Mark Sulkowski, MD along with Fred Poordad, MD, Nezam Afdhal, MD and K. Rajender Reddy, MD as they review and discuss the key new studies from EASL 2015.
Program Overview
The Advances in Chronic Hepatitis C: Management and Treatment program is a comprehensive, expert review of the 50th Annual Meeting of the European Association for the Study of the Liver (EASL 2015). This program consists of four components: (1) CME Internet Symposium: EASL 2015 Review: a 1.5 hour Internet symposium that features an overview and discussion of key presentations and posters, selected by the expert faculty discussants; (2) CME Internet Symposium: European Perspective on EASL 2015: a 1-hour Internet symposium featuring Europe-based expert faculty reviewing and discussing key presentations with a focus on management and treatment in the EU; (3) Rapid-Fire Review of EASL 2015: a podcast that provides a brief, audio summary of the most essential data presented at the conference; and (4) From Conference To Clinic: Reviewing And Applying Data From EASL 2015: case-based dinner meetings during which the key data are reviewed, discussed and applied to patient care.
The CME Internet Symposium: EASL 2015 Review will feature four HCV experts reviewing and discussing key presentations on chronic hepatitis C presented at EASL 2015. The review and discussion will focus on HCV therapeutic options and developments, including: current treatment and management strategies, algorithms and recommendations; therapies in development; epidemiology; and diagnosis and clinical management of specific patient populations, including HCV/HIV co-infected and cirrhotic patients.
This activity will enable participating health care providers caring for HCV-infected patients to become aware of and understand the data presented at this important conference and appropriately utilize those data to improve patient care. All online components of the program can be accessed at www.viraled.com.
This program is produced by the Postgraduate Institute for Medicine and ViralEd, Inc. It is not a session created by or presented at EASL 2015 and it is not sanctioned by the organizers of EASL 2015.
Wednesday, April 29, 2015
Benitec Doses Fifth Patient And Initiates Additional Trial Site For Hepatitis C Trial
Benitec Biopharma Doses Fifth Patient And Initiates Additional Trial Site For Hepatitis C Trial
- Third patient in cohort two dosed
- Total of five patients now dosed
- Third clinical trial site initiated - the Texas Liver Institute
- Future reporting of this trial to be on completion of trial or as a result of a material event
- Total of five patients now dosed
- Third clinical trial site initiated - the Texas Liver Institute
- Future reporting of this trial to be on completion of trial or as a result of a material event
SYDNEY, April 29, 2015 /PRNewswire/ -- Benitec Biopharma (ASX: BLT; OTCPK: BTEBY), a biopharmaceutical company focused on providing potentially curative therapies with its proprietary gene-silencing technology called ddRNAi or "expressed RNAi," is pleased to advise that the fifth patient in the company's 'first in man', Phase I/IIa dose escalation clinical trial of TT-034 for hepatitis C virus (HCV) infection, has today, been dosed at the Duke Clinical Research Unit. The fifth patient is the third and final patient to be dosed in Cohort 2.
The three patients in Cohort 2 received a dose of TT-034 of 1.25 x 10^11 vg/kg, a concentration that is a half log higher than the doses administered in Cohort 1. In line with the trial's primary endpoint of safety, this dose level is still below the concentration expected to inhibit HCV viral replication and data from the second dosing cohort is therefore expected to serve primarily as a further safety assessment.
As with previous patients, the newly dosed patient will be monitored for six weeks and this data will then be reviewed by the Data Safety Monitoring Board (DSMB). Benitec is currently screening patients for inclusion in cohort 3 in anticipation of the DSMB's review.
Benitec has now initiated a third site, the Texas Liver Institute in San Antonio, Texas, and they have started to pre-screen patients for the TT-034 trial.
Following completion of the first two patient cohorts and initiation of a third trial site, Benitec will now move to conventional clinical trial reporting for cohorts 3 through to 5 of the dose escalation study. The company will provide an update to investors (via ASX announcement) should a material event occur or when the trial is completed.
About TT-034
TT-034 is a ddRNAi-based therapeutic, designed to treat and potentially cure hepatitis C (HCV) with a single administration. TT-034 targets the hepatitis C viral RNA at three separate, highly conserved sites. As such it acts as a "triple therapy" even though it is a monotherapy, and minimises the ability of the virus to mutate and escape the therapy. Once it reaches the liver cells it enters the nucleus and produces three separate short hairpin RNAs continuously for the life time of the cell. Thus it has the potential to not only treat the existing HCV infection but to guard against reinfection for months to years without the need to re-treat. It has been extensively tested in pre-clinical in vivo studies and no adverse effects were seen at any therapeutic dose. However, as it is regulated as a gene therapy, the trial design is to primarily ensure that treatment with TT-034 is safe, hence the gradual dose escalation.
The three patients in Cohort 2 received a dose of TT-034 of 1.25 x 10^11 vg/kg, a concentration that is a half log higher than the doses administered in Cohort 1. In line with the trial's primary endpoint of safety, this dose level is still below the concentration expected to inhibit HCV viral replication and data from the second dosing cohort is therefore expected to serve primarily as a further safety assessment.
As with previous patients, the newly dosed patient will be monitored for six weeks and this data will then be reviewed by the Data Safety Monitoring Board (DSMB). Benitec is currently screening patients for inclusion in cohort 3 in anticipation of the DSMB's review.
Benitec has now initiated a third site, the Texas Liver Institute in San Antonio, Texas, and they have started to pre-screen patients for the TT-034 trial.
Following completion of the first two patient cohorts and initiation of a third trial site, Benitec will now move to conventional clinical trial reporting for cohorts 3 through to 5 of the dose escalation study. The company will provide an update to investors (via ASX announcement) should a material event occur or when the trial is completed.
About TT-034
TT-034 is a ddRNAi-based therapeutic, designed to treat and potentially cure hepatitis C (HCV) with a single administration. TT-034 targets the hepatitis C viral RNA at three separate, highly conserved sites. As such it acts as a "triple therapy" even though it is a monotherapy, and minimises the ability of the virus to mutate and escape the therapy. Once it reaches the liver cells it enters the nucleus and produces three separate short hairpin RNAs continuously for the life time of the cell. Thus it has the potential to not only treat the existing HCV infection but to guard against reinfection for months to years without the need to re-treat. It has been extensively tested in pre-clinical in vivo studies and no adverse effects were seen at any therapeutic dose. However, as it is regulated as a gene therapy, the trial design is to primarily ensure that treatment with TT-034 is safe, hence the gradual dose escalation.
Tuesday, April 28, 2015
Our Expert Picks: Critical Data From EASL 2015
2015 Meeting of the European Association for the Study of the Liver
Independent Conference Coverage*
Jordan J. Feld, MD, MPH
Kris V. Kowdley, MD, FACP, FACG, FASGE, AGAF
Andrew J. Muir, MD
David R. Nelson, MD
Norah Terrault, MD, MPH
Stefan Zeuzem, MD
The Capsule Summaries of the most important studies, as selected by the faculty members, are still being posted; the following are available to date.
Review Conference Coverage
Jordan J. Feld, MD, MPH
Kris V. Kowdley, MD, FACP, FACG, FASGE, AGAF
Andrew J. Muir, MD
David R. Nelson, MD
Norah Terrault, MD, MPH
Stefan Zeuzem, MD
The Capsule Summaries of the most important studies, as selected by the faculty members, are still being posted; the following are available to date.
Review Conference Coverage
Coming Soon: CME-certified Expert Analysis: Leading experts discuss the clinical implications of new data from the meeting in Vienna, Austria
Free registration is required
Capsule Summaries:
C-EDGE: Grazoprevir/Elbasvir Highly Effective in Treatment-Naive Patients With Genotype
1, 4, or 6 HCV Infection
High efficacy observed regardless of presence of cirrhosis, although patients with high baseline HCV RNA level were more likely to experience virologic failure.
Read More
ION-4: 96% SVR12 Rate With LDV/SOF for 12 Weeks in Patients Coinfected With HIV and Genotype 1 or 4 HCV
In multivariate analysis, black race only factor associated with treatment failure.
Read More
C-EDGE COINFECTION: 12 Weeks of Grazoprevir/Elbasvir Safe and Highly Effective in Genotype 1 and 4 HCV/HIV-Coinfected Patients
No HCV genotype/subtype or other patient parameter was associated with a decrease in treatment efficacy for this coinfected population.
Read More
High SVR12 Rate With Ledipasvir/Sofosbuvir Plus Ribavirin for 12 or 24 Weeks in GT1 or 4
HCV-Infected Patients With Decompensated Cirrhosis or HCV Recurrence After Liver Transplantation
In this population of patients with advanced liver disease, ledipasvir/sofosbuvir plus ribavirin treatment was generally safe and well tolerated with low rates of treatment-related serious adverse events and treatment discontinuation due to adverse events.
Read More
HCV-TARGET: High SVR12 Rates but More Frequent AEs Among Patients With Renal Dysfunction Treated With Sofosbuvir-Containing Regimens in Real-World Analysis
Rates of anemia-related AEs, worsening renal function, and renal and urinary AEs increased across patient groups with decreasing renal function.
Read More
C-SALVAGE: High SVR12 Rate Following 12 Weeks of Grazoprevir, Elbasvir, and Ribavirin in GT1 PI-Experienced Patients
The SVR12 rate in this PI-experienced population was 96% overall and 95% among patients with previous virologic failure; 3 patients relapsed with treatment-emergent NS3 and NS5A RAVs.
Read More
SVR12 in 71% of GT1 Patients Receiving 24 Weeks of Ledipasvir/Sofosbuvir Following Previous Treatment Failure With 8 or 12 Weeks of Ledipasvir/Sofosbuvir-Based Therapy
In this open-label trial, SVR12 rates were numerically lower in patients with vs without baseline NS5A RAVs and in patients who received 12 vs 8 weeks of previous ledipasvir/sofosbuvir-based therapy.
Read More
C-SCAPE: 12-Week Grazoprevir/Elbasvir Plus RBV Demonstrates Efficacy in Patients With Genotype 2 HCV Infection in Phase II Study
Efficacy also observed in genotype 4 HCV-infected patients receiving grazoprevir/elbasvir with or without ribavirin; evaluation of efficacy in genotypes 5 and 6 require additional patient numbers.
Read More
Sofosbuvir Plus Ledipasvir or Daclatasvir With or Without Ribavirin Effective in Patients With HCV Genotypes 1 and 3 and Decompensated Cirrhosis
In this observational cohort study, higher SVR12 rates with 12 weeks of sofosbuvir plus daclatasvir than sofosbuvir/ledipasvir among patients with genotype 3 HCV infection.
Read More
Interim Analysis: Early Efficacy With Sofosbuvir Plus Daclatasvir With or Without Ribavirin in Cirrhotic Patients With Genotype 3 HCV in Compassionate Use Program
In the subset of study patients who have reached SVR4, extended treatment duration of 24 weeks appeared to provide greater efficacy vs 12 weeks in this difficult-to-treat population.
Read More
High Incidence of HCV Reinfection Following SVR Among Patients Who Relapse to Injection Drug Use
Incidence of HCV reinfection 4.7/100 person-years among patients who relapsed to injection drug use vs 1.8/100 person-years among those with any previous injection drug use.
Read More
These Capsule Summaries are part of the program:
Clinical Impact of New Data From EASL 2015 clinicaloptions.com/vienna2015.
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
Capsule Summaries:
C-EDGE: Grazoprevir/Elbasvir Highly Effective in Treatment-Naive Patients With Genotype
1, 4, or 6 HCV Infection
High efficacy observed regardless of presence of cirrhosis, although patients with high baseline HCV RNA level were more likely to experience virologic failure.
Read More
ION-4: 96% SVR12 Rate With LDV/SOF for 12 Weeks in Patients Coinfected With HIV and Genotype 1 or 4 HCV
In multivariate analysis, black race only factor associated with treatment failure.
Read More
C-EDGE COINFECTION: 12 Weeks of Grazoprevir/Elbasvir Safe and Highly Effective in Genotype 1 and 4 HCV/HIV-Coinfected Patients
No HCV genotype/subtype or other patient parameter was associated with a decrease in treatment efficacy for this coinfected population.
Read More
High SVR12 Rate With Ledipasvir/Sofosbuvir Plus Ribavirin for 12 or 24 Weeks in GT1 or 4
HCV-Infected Patients With Decompensated Cirrhosis or HCV Recurrence After Liver Transplantation
In this population of patients with advanced liver disease, ledipasvir/sofosbuvir plus ribavirin treatment was generally safe and well tolerated with low rates of treatment-related serious adverse events and treatment discontinuation due to adverse events.
Read More
HCV-TARGET: High SVR12 Rates but More Frequent AEs Among Patients With Renal Dysfunction Treated With Sofosbuvir-Containing Regimens in Real-World Analysis
Rates of anemia-related AEs, worsening renal function, and renal and urinary AEs increased across patient groups with decreasing renal function.
Read More
C-SALVAGE: High SVR12 Rate Following 12 Weeks of Grazoprevir, Elbasvir, and Ribavirin in GT1 PI-Experienced Patients
The SVR12 rate in this PI-experienced population was 96% overall and 95% among patients with previous virologic failure; 3 patients relapsed with treatment-emergent NS3 and NS5A RAVs.
Read More
SVR12 in 71% of GT1 Patients Receiving 24 Weeks of Ledipasvir/Sofosbuvir Following Previous Treatment Failure With 8 or 12 Weeks of Ledipasvir/Sofosbuvir-Based Therapy
In this open-label trial, SVR12 rates were numerically lower in patients with vs without baseline NS5A RAVs and in patients who received 12 vs 8 weeks of previous ledipasvir/sofosbuvir-based therapy.
Read More
C-SCAPE: 12-Week Grazoprevir/Elbasvir Plus RBV Demonstrates Efficacy in Patients With Genotype 2 HCV Infection in Phase II Study
Efficacy also observed in genotype 4 HCV-infected patients receiving grazoprevir/elbasvir with or without ribavirin; evaluation of efficacy in genotypes 5 and 6 require additional patient numbers.
Read More
Sofosbuvir Plus Ledipasvir or Daclatasvir With or Without Ribavirin Effective in Patients With HCV Genotypes 1 and 3 and Decompensated Cirrhosis
In this observational cohort study, higher SVR12 rates with 12 weeks of sofosbuvir plus daclatasvir than sofosbuvir/ledipasvir among patients with genotype 3 HCV infection.
Read More
Interim Analysis: Early Efficacy With Sofosbuvir Plus Daclatasvir With or Without Ribavirin in Cirrhotic Patients With Genotype 3 HCV in Compassionate Use Program
In the subset of study patients who have reached SVR4, extended treatment duration of 24 weeks appeared to provide greater efficacy vs 12 weeks in this difficult-to-treat population.
Read More
High Incidence of HCV Reinfection Following SVR Among Patients Who Relapse to Injection Drug Use
Incidence of HCV reinfection 4.7/100 person-years among patients who relapsed to injection drug use vs 1.8/100 person-years among those with any previous injection drug use.
Read More
These Capsule Summaries are part of the program:
Clinical Impact of New Data From EASL 2015 clinicaloptions.com/vienna2015.
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
EASL2015-Sofosbuvir Plus Ribavirin Provides High SVR at 12 Weeks in HCV Genotypes 2 and 3
Sofosbuvir Plus Ribavirin Provides High Sustained Virological Response at 12 Weeks in Patients With Hepatitis C Virus Genotypes 2 and 3: Presented at EASL
By Chris Berrie
VIENNA, Austria -- April 27, 2015 -- Combinations of sofosbuvir plus ribavirin with and without pegylated-interferon alpha-2a (PEG-interferon) are well tolerated and provide high sustained virological response at 12 weeks (SVR12) in patients with hepatitis C virus (HCV) genotypes 2 and 3, according to results of an open-label, phase 3 study presented at the International Liver Congress, the 50th Annual Meeting of the European Association for the Study of the Liver (EASL).
Currently available interferon-free therapies provide relatively low SVR rates for patients with HCV genotype 3. Treatment combinations with sofosbuvir, ribavirin, and PEG-interferon, however, have more recently achieved SVR rates from 68% to 94% for HCV genotypes 2 and 3.
To investigate these options further, investigators for the BOSON study included treatment-experienced HCV genotype 2 with cirrhosis, and HCV genotype 3. “We enriched [the study] for genotype 3 cirrhosis and PEG-interferon/ribavirin failure,” explained lead investigator Graham Foster, PhD, Blizard Institute of Cell and Molecular Science, Queen Mary’s University of London, London, United Kingdom, speaking here on April 25.
Target patients were randomised to 1 of 3 arms: sofosbuvir plus ribavirin for 16 weeks (n = 196) or 24 (n = 199) weeks, or the same combination with PEG-interferon for 12 weeks (n = 197). All patients received sofosbuvir 400 mg daily and ribavirin 1000 to 1200 mg in a divided daily dose, with PEG-interferon administered by injection at 180 µg weekly.
The primary endpoint was SVR12 as HCV RNA <15 IU/mL (lower limit of quantification)
Overall, the SVR12 results for these 16-, 24-, and 12-week treatments were high, with significant benefits for the longer sofosbuvir plus ribavirin regime (72% vs 85%; P = .0013), which provided further significant improvement when combined with PEG-interferon in the shorter treatment regime (85% vs 93%; P = .023).
This finding was paralleled in the HCV genotype 3 data, specifically: 71% versus 84% (P < .001) and 84% versus 93% (P = .008). For the lower numbers of patients with HCV genotype 2, SVR12 was generally higher, with no significant differences: 87% versus 100% versus 94%, respectively.
Further analysing patients with HCV genotype 3, SVR12 was generally higher in patients without cirrhosis across the treatment groups (80% vs 87% vs 95%) than in those with cirrhosis (51% vs 79% vs 88%), and for treatment-naïve patients (77% vs 88% vs 95%) than for treatment-experienced patients (64% vs 80% vs 91%).
This finding was paralleled within the cohort of treatment-naïve patients without cirrhosis (83% vs 90% vs 96%) and with cirrhosis (57% vs 82% vs 91%), and within the cohort of treatment-experienced patients without cirrhosis (76% vs 82% vs 94%) and with cirrhosis (47% vs 77% vs 86%).
The safety analysis demonstrated similar levels of adverse events across the treatment groups (94% vs 95% vs 99%), with no specific safety worries for grade 3/4 adverse events (6% vs 4% vs 8%) or serious adverse events (4% vs 5% vs 6%).
In the laboratory analyses, there were increased rates of grade 3/4 adverse events with the addition of PEG-interferon (15% vs 15% vs 38%), as well as increased haemoglobin <10 g/dL (4% vs 6% vs 12%), and platelets <50,000/mm3 (<1% vs 0% vs 5%).
While all treatment regimens with all of these patient populations were well tolerated, with low rates of treatment discontinuation due to adverse events, Dr. Foster noted, “It seems that interferon may still have a role to play in some particular populations.”
Patient baseline characteristics in this study were well balanced across the treatment arms, with the full cohort showing a mean age of 50 years, 67% male, and a mean HCV RNA 6.3 log10 IU/mL. In all, 92% of patients had genotype 3, and the enrichment group included 37% patients with cirrhosis and 53% treatment-experienced patients.
Funding for this study was provided by Gilead Sciences, Foster City, California.
[Presentation title: Sofosbuvir Plus PEG-IFN/RBV for 12 Weeks vs Sofobuvir/RBV for 16 or 24 Weeks in Genotype 3 HCV-Infected Patients and Treatment-Experienced Cirrhotic Patients with Genotype 2 HCV: the BOSON Study. Abstract L05]
To read more Conference Dispatch articles, click here.
By Chris Berrie
VIENNA, Austria -- April 27, 2015 -- Combinations of sofosbuvir plus ribavirin with and without pegylated-interferon alpha-2a (PEG-interferon) are well tolerated and provide high sustained virological response at 12 weeks (SVR12) in patients with hepatitis C virus (HCV) genotypes 2 and 3, according to results of an open-label, phase 3 study presented at the International Liver Congress, the 50th Annual Meeting of the European Association for the Study of the Liver (EASL).
Currently available interferon-free therapies provide relatively low SVR rates for patients with HCV genotype 3. Treatment combinations with sofosbuvir, ribavirin, and PEG-interferon, however, have more recently achieved SVR rates from 68% to 94% for HCV genotypes 2 and 3.
To investigate these options further, investigators for the BOSON study included treatment-experienced HCV genotype 2 with cirrhosis, and HCV genotype 3. “We enriched [the study] for genotype 3 cirrhosis and PEG-interferon/ribavirin failure,” explained lead investigator Graham Foster, PhD, Blizard Institute of Cell and Molecular Science, Queen Mary’s University of London, London, United Kingdom, speaking here on April 25.
Target patients were randomised to 1 of 3 arms: sofosbuvir plus ribavirin for 16 weeks (n = 196) or 24 (n = 199) weeks, or the same combination with PEG-interferon for 12 weeks (n = 197). All patients received sofosbuvir 400 mg daily and ribavirin 1000 to 1200 mg in a divided daily dose, with PEG-interferon administered by injection at 180 µg weekly.
The primary endpoint was SVR12 as HCV RNA <15 IU/mL (lower limit of quantification)
Overall, the SVR12 results for these 16-, 24-, and 12-week treatments were high, with significant benefits for the longer sofosbuvir plus ribavirin regime (72% vs 85%; P = .0013), which provided further significant improvement when combined with PEG-interferon in the shorter treatment regime (85% vs 93%; P = .023).
This finding was paralleled in the HCV genotype 3 data, specifically: 71% versus 84% (P < .001) and 84% versus 93% (P = .008). For the lower numbers of patients with HCV genotype 2, SVR12 was generally higher, with no significant differences: 87% versus 100% versus 94%, respectively.
Further analysing patients with HCV genotype 3, SVR12 was generally higher in patients without cirrhosis across the treatment groups (80% vs 87% vs 95%) than in those with cirrhosis (51% vs 79% vs 88%), and for treatment-naïve patients (77% vs 88% vs 95%) than for treatment-experienced patients (64% vs 80% vs 91%).
This finding was paralleled within the cohort of treatment-naïve patients without cirrhosis (83% vs 90% vs 96%) and with cirrhosis (57% vs 82% vs 91%), and within the cohort of treatment-experienced patients without cirrhosis (76% vs 82% vs 94%) and with cirrhosis (47% vs 77% vs 86%).
The safety analysis demonstrated similar levels of adverse events across the treatment groups (94% vs 95% vs 99%), with no specific safety worries for grade 3/4 adverse events (6% vs 4% vs 8%) or serious adverse events (4% vs 5% vs 6%).
In the laboratory analyses, there were increased rates of grade 3/4 adverse events with the addition of PEG-interferon (15% vs 15% vs 38%), as well as increased haemoglobin <10 g/dL (4% vs 6% vs 12%), and platelets <50,000/mm3 (<1% vs 0% vs 5%).
While all treatment regimens with all of these patient populations were well tolerated, with low rates of treatment discontinuation due to adverse events, Dr. Foster noted, “It seems that interferon may still have a role to play in some particular populations.”
Patient baseline characteristics in this study were well balanced across the treatment arms, with the full cohort showing a mean age of 50 years, 67% male, and a mean HCV RNA 6.3 log10 IU/mL. In all, 92% of patients had genotype 3, and the enrichment group included 37% patients with cirrhosis and 53% treatment-experienced patients.
Funding for this study was provided by Gilead Sciences, Foster City, California.
[Presentation title: Sofosbuvir Plus PEG-IFN/RBV for 12 Weeks vs Sofobuvir/RBV for 16 or 24 Weeks in Genotype 3 HCV-Infected Patients and Treatment-Experienced Cirrhotic Patients with Genotype 2 HCV: the BOSON Study. Abstract L05]
To read more Conference Dispatch articles, click here.
Sunday, April 26, 2015
Single Pill Combination Therapy For Some Hepatitis C Subtypes
Single Pill Combination Therapy For Some Hepatitis C Subtypes
Posted on April 26, 2015
Source-
Posted on April 26, 2015
Source-
Interview with:
Stefan Zeuzem, MD
Professor of Medicine
Chief Department of Medicine
Goethe University Hospital
Frankfurt
Medical Research: What is the background for this study? What are the main findings?
Dr. Zeuzem: Interferon- and ribavirin-free regimens are needed to treat HCV infection. The objective of the study was to evaluate the safety and efficacy of grazoprevir (NS3/4A-protease-inhibitor) and elbasvir (NS5A-inhibitor) in previously untreated patients with chronic hepatitis C (without and with liver cirrhosis). Among 421 participants, 194 (46%) were women, 157 (37%) were non-white, 382 (91%) had genotype-1 infection, and 92 (22%) had cirrhosis.
Stefan Zeuzem, MD
Professor of Medicine
Chief Department of Medicine
Goethe University Hospital
Frankfurt
Medical Research: What is the background for this study? What are the main findings?
Dr. Zeuzem: Interferon- and ribavirin-free regimens are needed to treat HCV infection. The objective of the study was to evaluate the safety and efficacy of grazoprevir (NS3/4A-protease-inhibitor) and elbasvir (NS5A-inhibitor) in previously untreated patients with chronic hepatitis C (without and with liver cirrhosis). Among 421 participants, 194 (46%) were women, 157 (37%) were non-white, 382 (91%) had genotype-1 infection, and 92 (22%) had cirrhosis.
Of 316 patients receiving immediate treatment, 299/316 achieved SVR12 (undetectable HCV 12 weeks after treatment), including 144/157 with genotype-1a, 129/131 with genotype-1b, 18/18 with genotype-4, 8/10 with genotype-6, 68/70 with cirrhosis, and 231/246 without cirrhosis.
Virologic failure occurred in 13 patients including 1 breakthrough and 12 relapses, and was associated with baseline NS5A-polymorphisms and emergent NS3- and/or NS5A-variants. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo arms, respectively; none were considered drug-related.
Medical Research: What should clinicians and patients take away from your report?
Dr. Zeuzem: Various interferon-free regimen are available for patients with chronic hepatitis C. Grazoprevir and Elbasvir are co-formulated and will be the second available treatment regimen with a single pill per day. The new treatment is restricted to patients infected with HCV genotypes 1, 4, and 6. In previously untreated patient the addition of ribavirin to this regimen is not required
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Zeuzem: Future research should explore the higher virologic relapse rate in high-viraemic, HCV-1a infected patients with pre-existent resistance-associated variants against elbasvir. The requirement of molecular tests to test for these variants before initiation of theray should be carefully defined.
Citation:
Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic HCV Genotype 1, 4, or 6 Infection: A Randomized Trial
Stefan Zeuzem, MD; Reem Ghalib, MD; K. Rajender Reddy, MD; Paul J. Pockros, MD; Ziv Ben Ari, MD; Yue Zhao, PhD; Deborah D. Brown, BS; Shuyan Wan, PhD; Mark J. DiNubile, MD; Bach-Yen Nguyen, MD; Michael N. Robertson, MD; Janice Wahl, MD; Eliav Barr, MD; and Joan R. Butterton, MD
Ann Intern Med. Published online 24 April 2015 doi:10.7326/M15-0785
Medical Research: What should clinicians and patients take away from your report?
Dr. Zeuzem: Various interferon-free regimen are available for patients with chronic hepatitis C. Grazoprevir and Elbasvir are co-formulated and will be the second available treatment regimen with a single pill per day. The new treatment is restricted to patients infected with HCV genotypes 1, 4, and 6. In previously untreated patient the addition of ribavirin to this regimen is not required
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Zeuzem: Future research should explore the higher virologic relapse rate in high-viraemic, HCV-1a infected patients with pre-existent resistance-associated variants against elbasvir. The requirement of molecular tests to test for these variants before initiation of theray should be carefully defined.
Citation:
Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic HCV Genotype 1, 4, or 6 Infection: A Randomized Trial
Stefan Zeuzem, MD; Reem Ghalib, MD; K. Rajender Reddy, MD; Paul J. Pockros, MD; Ziv Ben Ari, MD; Yue Zhao, PhD; Deborah D. Brown, BS; Shuyan Wan, PhD; Mark J. DiNubile, MD; Bach-Yen Nguyen, MD; Michael N. Robertson, MD; Janice Wahl, MD; Eliav Barr, MD; and Joan R. Butterton, MD
Ann Intern Med. Published online 24 April 2015 doi:10.7326/M15-0785
Weekend Reading - EASL Updates and CCO Article:When Should Patients on the Liver Transplant Waitlist Receive HCV Therapy?
%2B(1).jpg)
Weekend Reading - When Should Patients on the Liver Transplant Waitlist Receive HCV Therapy?
Today we have a few EASL updates, but first up an article published at Clinical Care Opitions this past Friday; "When Should Patients on the Liver Transplant Waitlist Receive HCV Therapy?" by John Roberts, MD.
The good doctor offers us his expert opinion on which patients should receive HCV treatment before transplantation.
An excerpt;
Now that highly tolerable, highly effective HCV treatments are available, treatment in the pretransplant setting is a viable approach for many patients currently on the waitlist. Does this approach have a downside?
For transplantation candidates, the introduction of effective and tolerable HCV direct-acting antivirals has led to a challenging question: Who on the liver transplant waitlist should receive HCV therapy prior to transplantation and how can appropriate timing be achieved?
Read more, here
*Free registration is required to view content
What an exciting weekend, tons of research on hepatitis C is coming out of the 50th Annual Meeting of the European Association for the Study of the Liver (EASL 2015)
Over the next few weeks we can expect to find numerous media highlights of the meeting, but anyone living with HCV or considering therapy may want to dig a little deeper by reading in-depth coverage offered in an array of formats available online at "Clinical Care Options."
Where To Start
If you're in search of something self-explanatory, CCO has downloable slide-sets, easy to follow capsule summaries, and expert analysis. Coverage at CCO is ongoing, to get you started check out CCO's latest content.
Latest Content
SVR12 in 71% of GT1 Patients Receiving 24 Weeks of Ledipasvir/Sofosbuvir Following Previous Treatment Failure With 8 or 12 Weeks of Ledipasvir/Sofosbuvir-Based Therapy
In this open-label trial, SVR12 rates were numerically lower in patients with vs without baseline NS5A RAVs and in patients who received 12 vs 8 weeks of previous ledipasvir/sofosbuvir-based therapy.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/25/2015
C-EDGE: Grazoprevir/Elbasvir Highly Effective in Treatment-Naive Patients With Genotype 1, 4, or 6 HCV Infection
High efficacy observed regardless of presence of cirrhosis, although patients with high baseline HCV RNA level were more likely to experience virologic failure.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/25/2015
C-SCAPE: 12-Week Grazoprevir/Elbasvir Plus RBV Demonstrates Efficacy in Patients With Genotype 2 HCV Infection in Phase II Study
Efficacy also observed in genotype 4 HCV–infected patients receiving grazoprevir/elbasvir with or without ribavirin; evaluation of efficacy in genotypes 5 and 6 require additional patient numbers.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/25/2015
Sofosbuvir Plus Ledipasvir or Daclatasvir With or Without Ribavirin Effective in Patients With HCV Genotypes 1 and 3 and Decompensated Cirrhosis
In this observational cohort study, higher SVR12 rates with 12 weeks of sofosbuvir plus daclatasvir than sofosbuvir/ledipasvir among patients with genotype 3 HCV infection.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/24/2015
C-SALVAGE: High SVR12 Rate Following 12 Weeks of Grazoprevir, Elbasvir, and Ribavirin in GT1 PI-Experienced Patients
The SVR12 rate in this PI-experienced population was 96% overall and 95% among patients with previous virologic failure; 3 patients relapsed with treatment-emergent NS3 and NS5A RAVs.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/24/2015
Complete coverage is also available at the following websites.
In this open-label trial, SVR12 rates were numerically lower in patients with vs without baseline NS5A RAVs and in patients who received 12 vs 8 weeks of previous ledipasvir/sofosbuvir-based therapy.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/25/2015
C-EDGE: Grazoprevir/Elbasvir Highly Effective in Treatment-Naive Patients With Genotype 1, 4, or 6 HCV Infection
High efficacy observed regardless of presence of cirrhosis, although patients with high baseline HCV RNA level were more likely to experience virologic failure.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/25/2015
C-SCAPE: 12-Week Grazoprevir/Elbasvir Plus RBV Demonstrates Efficacy in Patients With Genotype 2 HCV Infection in Phase II Study
Efficacy also observed in genotype 4 HCV–infected patients receiving grazoprevir/elbasvir with or without ribavirin; evaluation of efficacy in genotypes 5 and 6 require additional patient numbers.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/25/2015
Sofosbuvir Plus Ledipasvir or Daclatasvir With or Without Ribavirin Effective in Patients With HCV Genotypes 1 and 3 and Decompensated Cirrhosis
In this observational cohort study, higher SVR12 rates with 12 weeks of sofosbuvir plus daclatasvir than sofosbuvir/ledipasvir among patients with genotype 3 HCV infection.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/24/2015
C-SALVAGE: High SVR12 Rate Following 12 Weeks of Grazoprevir, Elbasvir, and Ribavirin in GT1 PI-Experienced Patients
The SVR12 rate in this PI-experienced population was 96% overall and 95% among patients with previous virologic failure; 3 patients relapsed with treatment-emergent NS3 and NS5A RAVs.
Source: 2015 Annual Meeting of the European Association for the Study of the Liver
Date Posted: 4/24/2015
Complete coverage is also available at the following websites.
Slide presentations and commentary
Healio
Live Coverage
Medscape
Read clinically focused news coverage of key developments from EASL 2015.
HIV and Hepatitis
Look for breaking news coverage from HIV and Hepatitis and our partners at Aidsmap.com
Coming Soon
EASL In The News
Single Pill Combination Therapy For Some Hepatitis C Subtypes
Single Pill Combination Therapy For Some Hepatitis C Subtypes
Interferon- and ribavirin-free regimens are needed to treat HCV infection. The objective of the study was to evaluate the safety and efficacy of grazoprevir (NS3/4A-protease-inhibitor) and elbasvir (NS5A-inhibitor) in previously untreated patients with chronic hepatitis C(without and with liver cirrhosis).
Interferon Tx Scores in Tough-to-Treat HCV
Demonized drug performs well in genotype 3 of hepatitis C.
Hepatitis C screening essential to help catch patients with advanced liver fibrosis
Cancer rates among patients with hepatitis C are increased compared to those not infected
The aim of the study was to describe the rates of all cancers in the cohort of HCV patients compared to the non-HCV population. Known cancer types associated with hepatitis C include non-Hodgkin's lymphoma, renal and prostate cancers, as well as liver cancer.
The aim of the study was to describe the rates of all cancers in the cohort of HCV patients compared to the non-HCV population. Known cancer types associated with hepatitis C include non-Hodgkin's lymphoma, renal and prostate cancers, as well as liver cancer.
April 25
BOSON: Sovaldi plus PEG-RBV improved SVR12 in genotype 3 HCV
Twelve weeks of therapy with Sovaldi plus peginterferon and ribavirin was associated with 12-week sustained virologic response rates…
ALLY-1 Trial Results Show Investigational Daclatasvir-Based Regimen Cures 94% of Post-Liver Transplant Patients with Hepatitis C and Up to 94% of Hepatitis C Patients with Cirrhosis (Child-Pugh Class A or B)
97% of post-transplant patients with HCV genotype 1a achieved cure
91% of post-transplant patients with HCV genotype 3 achieved cure
No need seen to alter existing transplantation medication regimens
Gilead Announces Results From Studies Evaluating Sofosbuvir-Based Regimens in Chronic Hepatitis C Patients With Genotypes 2-5
-- High Cure Rates Observed Across a Range of Genotypes --
VIENNA, Austria--(BUSINESS WIRE)--Apr. 25, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two studies evaluating the safety and efficacy of investigational uses of sofosbuvir-based regimens in chronic hepatitis C virus (HCV)-infected patients with genotypes 2, 3, 4 and 5. Results from the BOSON study of Sovaldi® (sofosbuvir 400 mg) in combination with ribavirin (RBV) or with pegylated interferon (PEG)/RBV demonstrated high cure rates across all patients with genotypes 2 and 3. Separately, results from a Phase 2 study demonstrate the safety and efficacy of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) in patients with genotypes 4 or 5 infection. Data from both studies will be presented in oral sessions at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria.
ABBVIE PRESENTS LATE-BREAKING, PRELIMINARY PHASE 3B DATA WITH VIEKIRAX® + EXVIERA® IN HCV PATIENTS W-RENAL IMPAIRMENT
- RUBY-I EVALUATES TREATMENT-NAÏVE, NON-CIRRHOTIC, GENOTYPE 1 CHRONIC HEPATITIS C PATIENTS WITH SEVERE RENAL IMPAIRMENT
- IN PRELIMINARY DATA FROM RUBY-I, PATIENTS RECEIVING VIEKIRAX + EXVIERA WITH OR WITHOUT RIBAVIRIN WHO REACHED POST-TREATMENT WEEK FOUR (N=10 OF 20 ENROLLED) ACHIEVED 100 PERCENT SUSTAINED VIROLOGIC RESPONSE AT FOUR WEEKS POST-TREATMENT (SVR4)1
- ABBVIE'S PHASE 3B STUDIES EXPLORE VIEKIRAX + EXVIERA IN ADDITIONAL PATIENT POPULATIONS SEEN IN CLINICAL PRACTICE AND ACROSS MULTIPLE COUNTRIES AROUND THE WORLD
Merck Announces Presentation of Phase 2 Clinical Trial Results of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir at the International Liver Congress™ 2015
Results of C-SALVAGE Study Showed High Sustained Virologic Response Rates in Patients Who Failed Prior Combination Therapy with Certain Direct Acting Antiviral (DAA) Agents
Results of C-SWIFT Study Provide Proof-of-Concept for Shorter Than Twelve Weeks Duration of Treatment with Triple-DAA Regimen in Patients with Chronic Hepatitis C Virus (HCV) Genotypes 1 and 3 Infection
Merck’s Pivotal Phase 3 C-EDGE Program Evaluating Grazoprevir/Elbasvir Shows High Sustained Virologic Responses Across Broad Range of Patients with Chronic Hepatitis C Virus Infection
Data Sets Include Treatment-Naïve, Treatment-Experienced and HIV Co-Infected Patients with Chronic Hepatitis C Virus Genotypes 1, 4 or 6 Infection
Merck Remains on Track to Submit New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) in First Half of 2015
Interferon Tx Scores in Tough-to-Treat HCVDemonized drug performs well in genotype 3 of hepatitis C.
VIENNA -- Rumors of the death of pegylated interferon may have been exaggerated.
In a surprising result, the widely demonized immune system booster came up trumps as therapy for patients with the difficult-to-treat genotype 3 hepatitis C (HCV), according to Kosh Agarwal, MD, of Kings College Hospital in London.
Once-Daily Oral Combination Clears Hepatitis C in 95%
Medscape Medical News, April 24, 2015
April 24
Merck oral hepatitis C regimen shows 95 pct cure rate
(Reuters) - Merck and Co Inc presented trial results on Friday showing that a once-daily combination of two experimental pills cured 95 percent of previously untreated hepatitis C patients after 12 weeks.
Press Release
Merck Announces Results from Phase 2/3 Study of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir in Patients with Advanced Chronic Kidney Disease
C-SURFER Trial is First to Investigate an All-Oral Ribavirin-Free Hepatitis C Treatment Regimen in Treatment-Naïve and Treatment-Experienced Patients with Advanced Chronic Kidney Disease Infected with Hepatitis C Virus Genotype 1
Patients feel stigma, discrimination when living with hepatitis
Merck’s Hepatitis C Medicines May Challenge Gilead and AbbVie
Two Diabetes Drugs May Ease Fatty Liver Disease
Cancer rates among patients with hepatitis C are increased compared to those not infected
April 23
Merck and Gilead square off in battle of the next-next-gen hep C combos
By John Carroll
Early today both Gilead and Merck issued new data on their next-next-gen hepatitis C combos, demonstrating just how brutal the competition for market share is becoming while highlighting some of the boundaries that are emerging in shortening treatment regimens.
Watch the body defend against attack from the hepatitis B virus
EASL Young Investigator, Matteo Iannacone, discusses the impact of a new pioneering technique – intravital microscopy, which allows scientists to observe real-time cell behaviour in a liver infected with hepatitis B.
Read full article and watch videos at www.lastampa.it
Liver
April 25
Lifestyle-induced weight loss produces improvement in NASH, fibrosis
VIENNA — Weight loss induced through year-long lifestyle intervention independently predicted improvement in non-alcoholic steatohepatitis, non-alcoholic steatosis and fibrosis, according to a study presented at the 2015 International Liver Congress.
“Weight loss induced by a comprehensive lifestyle program during 12 months produces important changes in most of the histological NASH-related features,” Eduardo Vilar-Gomez, MD, from the National Institute of Gastroenterology, Havana, Cuba, said during his presentation. “Our findings support the current recommendation for weight loss lifestyle modification as the first-line therapy for patients with NASH.”
Statins Show Benefit in Hepatitis C Compensated Cirrhosis
Medscape Medical News, April 25, 2015
Fatty Liver Disease Surging as Liver Cancer Cause
Medscape Medical News, April 25, 2015
April 24
VIDEO: 2DMRE accurately predicts advanced fibrosis in patients with NAFLD
April 24, 2015VIENNA — Jeffrey Y. Cui, fourth year medical student in the NAFLD Translational Research Unit at University of California San Diego School of…
BOSON: Sovaldi plus PEG-RBV improved SVR12 in genotype 3 HCV
Twelve weeks of therapy with Sovaldi plus peginterferon and ribavirin was associated with 12-week sustained virologic response rates…
ALLY-1 Trial Results Show Investigational Daclatasvir-Based Regimen Cures 94% of Post-Liver Transplant Patients with Hepatitis C and Up to 94% of Hepatitis C Patients with Cirrhosis (Child-Pugh Class A or B)
97% of post-transplant patients with HCV genotype 1a achieved cure
91% of post-transplant patients with HCV genotype 3 achieved cure
No need seen to alter existing transplantation medication regimens
Gilead Announces Results From Studies Evaluating Sofosbuvir-Based Regimens in Chronic Hepatitis C Patients With Genotypes 2-5
-- High Cure Rates Observed Across a Range of Genotypes --
VIENNA, Austria--(BUSINESS WIRE)--Apr. 25, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two studies evaluating the safety and efficacy of investigational uses of sofosbuvir-based regimens in chronic hepatitis C virus (HCV)-infected patients with genotypes 2, 3, 4 and 5. Results from the BOSON study of Sovaldi® (sofosbuvir 400 mg) in combination with ribavirin (RBV) or with pegylated interferon (PEG)/RBV demonstrated high cure rates across all patients with genotypes 2 and 3. Separately, results from a Phase 2 study demonstrate the safety and efficacy of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) in patients with genotypes 4 or 5 infection. Data from both studies will be presented in oral sessions at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria.
ABBVIE PRESENTS LATE-BREAKING, PRELIMINARY PHASE 3B DATA WITH VIEKIRAX® + EXVIERA® IN HCV PATIENTS W-RENAL IMPAIRMENT
- RUBY-I EVALUATES TREATMENT-NAÏVE, NON-CIRRHOTIC, GENOTYPE 1 CHRONIC HEPATITIS C PATIENTS WITH SEVERE RENAL IMPAIRMENT
- IN PRELIMINARY DATA FROM RUBY-I, PATIENTS RECEIVING VIEKIRAX + EXVIERA WITH OR WITHOUT RIBAVIRIN WHO REACHED POST-TREATMENT WEEK FOUR (N=10 OF 20 ENROLLED) ACHIEVED 100 PERCENT SUSTAINED VIROLOGIC RESPONSE AT FOUR WEEKS POST-TREATMENT (SVR4)1
- ABBVIE'S PHASE 3B STUDIES EXPLORE VIEKIRAX + EXVIERA IN ADDITIONAL PATIENT POPULATIONS SEEN IN CLINICAL PRACTICE AND ACROSS MULTIPLE COUNTRIES AROUND THE WORLD
Merck Announces Presentation of Phase 2 Clinical Trial Results of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir at the International Liver Congress™ 2015
Results of C-SALVAGE Study Showed High Sustained Virologic Response Rates in Patients Who Failed Prior Combination Therapy with Certain Direct Acting Antiviral (DAA) Agents
Results of C-SWIFT Study Provide Proof-of-Concept for Shorter Than Twelve Weeks Duration of Treatment with Triple-DAA Regimen in Patients with Chronic Hepatitis C Virus (HCV) Genotypes 1 and 3 Infection
Merck’s Pivotal Phase 3 C-EDGE Program Evaluating Grazoprevir/Elbasvir Shows High Sustained Virologic Responses Across Broad Range of Patients with Chronic Hepatitis C Virus Infection
Data Sets Include Treatment-Naïve, Treatment-Experienced and HIV Co-Infected Patients with Chronic Hepatitis C Virus Genotypes 1, 4 or 6 Infection
Merck Remains on Track to Submit New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) in First Half of 2015
Interferon Tx Scores in Tough-to-Treat HCVDemonized drug performs well in genotype 3 of hepatitis C.
VIENNA -- Rumors of the death of pegylated interferon may have been exaggerated.
In a surprising result, the widely demonized immune system booster came up trumps as therapy for patients with the difficult-to-treat genotype 3 hepatitis C (HCV), according to Kosh Agarwal, MD, of Kings College Hospital in London.
Once-Daily Oral Combination Clears Hepatitis C in 95%
Medscape Medical News, April 24, 2015
April 24
Merck oral hepatitis C regimen shows 95 pct cure rate
(Reuters) - Merck and Co Inc presented trial results on Friday showing that a once-daily combination of two experimental pills cured 95 percent of previously untreated hepatitis C patients after 12 weeks.
Press Release
Merck Announces Results from Phase 2/3 Study of Investigational Chronic Hepatitis C Therapy Grazoprevir/Elbasvir in Patients with Advanced Chronic Kidney Disease
C-SURFER Trial is First to Investigate an All-Oral Ribavirin-Free Hepatitis C Treatment Regimen in Treatment-Naïve and Treatment-Experienced Patients with Advanced Chronic Kidney Disease Infected with Hepatitis C Virus Genotype 1
Patients feel stigma, discrimination when living with hepatitis
Merck’s Hepatitis C Medicines May Challenge Gilead and AbbVie
Two Diabetes Drugs May Ease Fatty Liver Disease
Cancer rates among patients with hepatitis C are increased compared to those not infected
April 23
Merck and Gilead square off in battle of the next-next-gen hep C combos
By John Carroll
Early today both Gilead and Merck issued new data on their next-next-gen hepatitis C combos, demonstrating just how brutal the competition for market share is becoming while highlighting some of the boundaries that are emerging in shortening treatment regimens.
Watch the body defend against attack from the hepatitis B virus
EASL Young Investigator, Matteo Iannacone, discusses the impact of a new pioneering technique – intravital microscopy, which allows scientists to observe real-time cell behaviour in a liver infected with hepatitis B.
Read full article and watch videos at www.lastampa.it
April 25
Lifestyle-induced weight loss produces improvement in NASH, fibrosis
VIENNA — Weight loss induced through year-long lifestyle intervention independently predicted improvement in non-alcoholic steatohepatitis, non-alcoholic steatosis and fibrosis, according to a study presented at the 2015 International Liver Congress.
“Weight loss induced by a comprehensive lifestyle program during 12 months produces important changes in most of the histological NASH-related features,” Eduardo Vilar-Gomez, MD, from the National Institute of Gastroenterology, Havana, Cuba, said during his presentation. “Our findings support the current recommendation for weight loss lifestyle modification as the first-line therapy for patients with NASH.”
Statins Show Benefit in Hepatitis C Compensated Cirrhosis
Medscape Medical News, April 25, 2015
Fatty Liver Disease Surging as Liver Cancer Cause
Medscape Medical News, April 25, 2015
April 24
VIDEO: 2DMRE accurately predicts advanced fibrosis in patients with NAFLD
April 24, 2015VIENNA — Jeffrey Y. Cui, fourth year medical student in the NAFLD Translational Research Unit at University of California San Diego School of…
Hepatitis C screening essential to help catch patients with advanced liver fibrosis
Hepatitis C screening essential to help catch patients with advanced liver fibrosis
Research validates the current recommendation that screening for hepatitis C, particularly among high-risk groups, is vital.
April 25, 2015, Vienna, Austria: Study results presented today at The International Liver Congress™ 2015 show that the occurrence of advanced liver fibrosis is similar for patients infected with the hepatitis C virus (HCV), whether or not they have been diagnosed.
Most individuals with HCV remain asymptomatic, which makes the diagnosis difficult. The study authors used the hypothesis that individuals whose HCV is not diagnosed are less likely to have advanced fibrosis than those who have been diagnosed. They then compared liver fibrosis between respondents of the National Health and Nutrition Examination Survey (NHANES) in the USA, in patients with diagnosed and undiagnosed HCV infection.
Of the respondents with known HCV infection, the proportion with a high, intermediate and low probability of advanced fibrosis was 14.5%, 40.3%, 45.2%, respectively; in those with undiagnosed HCV the results were 19.1%, 30.9%, 50.0%, respectively.
The study highlights that even if people are unaware they are infected with HCV, the virus affects their liver in the same way, resulting in advanced fibrosis. These results validate the current recommendation that screening for HCV, particularly among high-risk groups, is vital.
###
About The International Liver Congress™
This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.
About EASL
Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
Contact
For more information, please contact the ILC Press Office at:
ilc.press@easloffice.eu or
+44 (0)20 3580 5444
EU and Public Health: Hall C (Plenary) Presentation time: 11:30 - 11:45 Presenter: Prowpanga Udompap (United States) Abstract O120: ADVANCED FIBROSIS IS COMMON IN INDIVIDUALS WHOSE HEPATITIS C HAS NOT BEEN DIAGNOSED: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2001-2012
ADVANCED FIBROSIS IS COMMON IN INDIVIDUALS WHOSE HEPATITIS C HAS NOT BEEN DIAGNOSED: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2001-2012
Prowpanga Udompap* 1, Ajitha Mannalithara1, Nae-Yun Heo1, W. Ray Kim1 1Division of Gastroenterology and Hepatology, Stanford University, Stanford, United States
Background and Aims: Hepatitis C virus (HCV) infection is a global public health problem - while it is common, its consequences may be severe, including end stage liver disease and hepatocellular carcinoma. Moreover, most individuals with HCV remain asymptomatic, which makes the diagnosis difficult. With the hypothesis that individuals whose HCV is not diagnosed are less likely to have advanced fibrosis than those who have been diagnosed, we compare liver fibrosis between respondents to the National Health and Nutrition Examination Survey (NHANES) with diagnosed and undiagnosed HCV infection.
Methods: Testing for HCV was incorporated in NHANES 2001-2012. In a subgroup of the respondents with HCV infection, follow-up questionnaires were administered. Awareness of HCV infection was assessed by the question whether they had known they had HCV before receiving a letter from NHANES. Liver fibrosis was estimated by the FIB-4 and APRI scores. Based on the published cut-off values for advanced fibrosis, the proportion of respondents with a high probability of advanced fibrosis was compared between respondents with known and undiagnosed HCV.
Results: Out of 30,140 respondents of the NHANES survey, 360 tested positive for HCV RNA. There were 355 participants with complete laboratory data needed for the FIB-4 and APRI scores, of whom 130 had completed the full hepatitis C follow-up questionnaires. Slightly less than half (47.7%, n=62) knew that they had hepatitis C infection before the survey, whereas in the remainder (52.3%), HCV was only discovered from the survey. In the figure, the two groups were comparable with respect to age, sex, aminotransferase and platelet counts. BMI was higher in those with known diagnosed, the significance of which is uncertain. The raw FIB-4 and APRI scores were similar between the two groups. Among the respondents with known HCV infection, the proportion with a high, intermediate, and low probability of advanced fibrosis was 14.5%, 40.3%, 45.2%, respectively. The corresponding data in those with undiagnosed HCV were 19.1%, 30.9%, 50.0%, respectively. A similar pattern was seen with the APRI score.
Conclusions: While more than half of survey respondents did not know of their HCV infection, their liver fibrosis was no less advanced than those whose HCV had been diagnosed prior to participation in the survey. These data further justifies the current recommendation for HCV screening in asymptomatic individuals.
Disclosure of Interest: P. Udompap: : None Declared, A. Mannalithara: : None Declared, N.-Y. Heo: : None Declared, W. R. Kim: Consultant: Gilead, BMS
Research validates the current recommendation that screening for hepatitis C, particularly among high-risk groups, is vital.
April 25, 2015, Vienna, Austria: Study results presented today at The International Liver Congress™ 2015 show that the occurrence of advanced liver fibrosis is similar for patients infected with the hepatitis C virus (HCV), whether or not they have been diagnosed.
Most individuals with HCV remain asymptomatic, which makes the diagnosis difficult. The study authors used the hypothesis that individuals whose HCV is not diagnosed are less likely to have advanced fibrosis than those who have been diagnosed. They then compared liver fibrosis between respondents of the National Health and Nutrition Examination Survey (NHANES) in the USA, in patients with diagnosed and undiagnosed HCV infection.
Of the respondents with known HCV infection, the proportion with a high, intermediate and low probability of advanced fibrosis was 14.5%, 40.3%, 45.2%, respectively; in those with undiagnosed HCV the results were 19.1%, 30.9%, 50.0%, respectively.
The study highlights that even if people are unaware they are infected with HCV, the virus affects their liver in the same way, resulting in advanced fibrosis. These results validate the current recommendation that screening for HCV, particularly among high-risk groups, is vital.
###
About The International Liver Congress™
This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.
About EASL
Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.
Contact
For more information, please contact the ILC Press Office at:
ilc.press@easloffice.eu or
+44 (0)20 3580 5444
EU and Public Health: Hall C (Plenary) Presentation time: 11:30 - 11:45 Presenter: Prowpanga Udompap (United States) Abstract O120: ADVANCED FIBROSIS IS COMMON IN INDIVIDUALS WHOSE HEPATITIS C HAS NOT BEEN DIAGNOSED: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2001-2012
ADVANCED FIBROSIS IS COMMON IN INDIVIDUALS WHOSE HEPATITIS C HAS NOT BEEN DIAGNOSED: RESULTS FROM THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY 2001-2012
Prowpanga Udompap* 1, Ajitha Mannalithara1, Nae-Yun Heo1, W. Ray Kim1 1Division of Gastroenterology and Hepatology, Stanford University, Stanford, United States
Background and Aims: Hepatitis C virus (HCV) infection is a global public health problem - while it is common, its consequences may be severe, including end stage liver disease and hepatocellular carcinoma. Moreover, most individuals with HCV remain asymptomatic, which makes the diagnosis difficult. With the hypothesis that individuals whose HCV is not diagnosed are less likely to have advanced fibrosis than those who have been diagnosed, we compare liver fibrosis between respondents to the National Health and Nutrition Examination Survey (NHANES) with diagnosed and undiagnosed HCV infection.
Methods: Testing for HCV was incorporated in NHANES 2001-2012. In a subgroup of the respondents with HCV infection, follow-up questionnaires were administered. Awareness of HCV infection was assessed by the question whether they had known they had HCV before receiving a letter from NHANES. Liver fibrosis was estimated by the FIB-4 and APRI scores. Based on the published cut-off values for advanced fibrosis, the proportion of respondents with a high probability of advanced fibrosis was compared between respondents with known and undiagnosed HCV.
Results: Out of 30,140 respondents of the NHANES survey, 360 tested positive for HCV RNA. There were 355 participants with complete laboratory data needed for the FIB-4 and APRI scores, of whom 130 had completed the full hepatitis C follow-up questionnaires. Slightly less than half (47.7%, n=62) knew that they had hepatitis C infection before the survey, whereas in the remainder (52.3%), HCV was only discovered from the survey. In the figure, the two groups were comparable with respect to age, sex, aminotransferase and platelet counts. BMI was higher in those with known diagnosed, the significance of which is uncertain. The raw FIB-4 and APRI scores were similar between the two groups. Among the respondents with known HCV infection, the proportion with a high, intermediate, and low probability of advanced fibrosis was 14.5%, 40.3%, 45.2%, respectively. The corresponding data in those with undiagnosed HCV were 19.1%, 30.9%, 50.0%, respectively. A similar pattern was seen with the APRI score.
Conclusions: While more than half of survey respondents did not know of their HCV infection, their liver fibrosis was no less advanced than those whose HCV had been diagnosed prior to participation in the survey. These data further justifies the current recommendation for HCV screening in asymptomatic individuals.
Disclosure of Interest: P. Udompap: : None Declared, A. Mannalithara: : None Declared, N.-Y. Heo: : None Declared, W. R. Kim: Consultant: Gilead, BMS
Saturday, April 25, 2015
Achillion Presents Results on ACH-3102 and ACH-3422 at EASL
Achillion Presents Detailed Clinical Results on ACH-3102 and ACH-3422 at the International Liver Congress
VIENNA, Austria, April 25, 2015 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today presented two late breaker posters at the 50th Annual Meeting of the European Association for the Study of the Liver (EASL) during The International Liver Congress 2015.
"We believe that the ability to achieve 100% SVR12 after six-weeks of treatment with ACH-3102 and sofosbuvir supports the potential for our proprietary doublet regimen to reduce treatment duration for HCV patients," commented Milind Deshpande, Ph.D., President and Chief Executive Officer of Achillion. "We are also very pleased with the robust Phase 1 proof-of-concept data reported on ACH-3422, our proprietary NS5B nucleotide polymerase inhibitor, and the clinical virology presentation that continues to support the differentiated higher barrier to resistance for ACH-3102."
Data highlights from all of the presentations include:
LP06: Sustained virologic response after ACH-3102 and sofosbuvir treatment for 8 or 6 weeks: A phase 2 "proxy" study ACH102-017. ePoster Presentation, April 25, 3:30 pm CET, Hall B ePoster Area. Lead Author: Edward Gane.
The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 150 million people are infected with HCV worldwide including more than 5 million people in the United States. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death.
About Achillion Pharmaceuticals
Achillion is seeking to apply its expertise in biology and structure-guided design and a deep understanding of patient and clinician needs to develop innovative treatment solutions aimed at improving patients' lives. The Company believes that its scientific excellence, integrated capabilities and experienced team position it to successfully achieve its goal of advancing new products along the entire continuum from the bench to the patient. Achillion's pipeline is currently focused on small molecule therapeutics for infectious disease and complement-related diseases. www.achillion.com
Cautionary Note Regarding Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including without limitation statements with respect to: the potential to create shorter treatments for HCV patients and the potential therapeutic and other benefits of ACH-3422 and ACH-3102. Achillion may use words such as "expect," "anticipate," "project," "intend," "plan," "aim," "believe," "seek," " estimate," "can," "focus," "will," and "may" and similar expressions to identify such forward-looking statements.
Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; advance the preclinical and clinical development of its drug candidates, including ACH-3102, ACH-3422, and sovaprevir, under the timelines it projects in current and future clinical trials; obtain and maintain necessary regulatory approvals; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; manage litigation; raise the substantial additional capital needed to achieve its business objectives; and successfully execute on its business strategies.
These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2014, and its subsequent SEC filings.
In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.
- Two late breaker presentations detail previously announced 100% SVR12 in Phase 2 trial evaluating 6- or 8-weeks of treatment with ACH-3102 and sofosbuvir in genotype 1 HCV patients and Phase 1 proof-of-concept results with ACH-3422 -
- Clinical virology presentation continues to support improved barrier to resistance with ACH-3102 -
"We believe that the ability to achieve 100% SVR12 after six-weeks of treatment with ACH-3102 and sofosbuvir supports the potential for our proprietary doublet regimen to reduce treatment duration for HCV patients," commented Milind Deshpande, Ph.D., President and Chief Executive Officer of Achillion. "We are also very pleased with the robust Phase 1 proof-of-concept data reported on ACH-3422, our proprietary NS5B nucleotide polymerase inhibitor, and the clinical virology presentation that continues to support the differentiated higher barrier to resistance for ACH-3102."
Data highlights from all of the presentations include:
LP06: Sustained virologic response after ACH-3102 and sofosbuvir treatment for 8 or 6 weeks: A phase 2 "proxy" study ACH102-017. ePoster Presentation, April 25, 3:30 pm CET, Hall B ePoster Area. Lead Author: Edward Gane.
- As previously reported, 100% of patients achieved SVR12 after six- (n=12) or eight-weeks (n=12) of treatment in this ongoing interferon-free, ribavirin-free study evaluating the efficacy, safety, and tolerability of 50 mg of ACH-3102 and 400 mg of sofosbuvir, a marketed nucleotide polymerase inhibitor, in treatment-naïve genotype 1 HCV-infected patients.
- This represents the first study to report 100% SVR12 in patients with chronic GT-1 HCV infection using a two-drug combination for 6 weeks.
- Complete virologic responses were seen in all patients, including those who were considered harder to treat than others (i.e. GT-1a, non-CC and VL > 6 million IU/mL).
- The combination of ACH-3102 with sofosbuvir was well tolerated, with no treatment discontinuations, a low incidence of AEs, and no reported significant AEs or SAEs during the treatment and follow-up periods.
- The present study provides support for future studies which will explore the use of ACH-3102 in sofosbuvir-sparing regimens with short-treatment durations.
- In parallel, further studies will explore the combination of ACH-3102 and ACH-3422 (with and without sovaprevir, an NS3 protease inhibitor) in interferon- and ribavirin-free regimens with short treatment durations across different patient populations.
- As previously announced, ACH-3422 achieved dose-related virologic responses in GT-1 HCV-infected patients. In the six patients who received 700 mg once daily for 14 days, mean maximal reduction from baseline was 4.6 log10, including three patients with target not detected.
- In all healthy volunteers and patients infected with HCV who received active treatment through 700 mg once daily, ACH-3422 was well-tolerated with no treatment-related serious adverse events, adverse event-related discontinuations, or clinically significant laboratory or ECG abnormalities.
- These results support further investigation of ACH-3422 with ACH-3102, a potent NS5A inhibitor, with or without the NS3/4A protease inhibitor sovaprevir, for the treatment of different patient populations with chronic HCV infection.
- Dominant NS5A variants found at baseline conferred significant resistance to ledipasvir and daclatasvir but not to ACH-3102, highlighting the mechanism underlying the improved clinical efficacy of ACH-3102.
- The clinical efficacy of ACH-3102 is also supported by its greater potency in vitro against a spectrum of GT-1a and -1b NS5A mutants as compared to the first generation of NS5A inhibitors.
- These data support further clinical exploration of ACH-3102.
The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 150 million people are infected with HCV worldwide including more than 5 million people in the United States. Three-fourths of the HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death.
About Achillion Pharmaceuticals
Achillion is seeking to apply its expertise in biology and structure-guided design and a deep understanding of patient and clinician needs to develop innovative treatment solutions aimed at improving patients' lives. The Company believes that its scientific excellence, integrated capabilities and experienced team position it to successfully achieve its goal of advancing new products along the entire continuum from the bench to the patient. Achillion's pipeline is currently focused on small molecule therapeutics for infectious disease and complement-related diseases. www.achillion.com
Cautionary Note Regarding Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including without limitation statements with respect to: the potential to create shorter treatments for HCV patients and the potential therapeutic and other benefits of ACH-3422 and ACH-3102. Achillion may use words such as "expect," "anticipate," "project," "intend," "plan," "aim," "believe," "seek," " estimate," "can," "focus," "will," and "may" and similar expressions to identify such forward-looking statements.
Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: demonstrate in any current and future clinical trials the requisite safety, efficacy and combinability of its drug candidates; advance the preclinical and clinical development of its drug candidates, including ACH-3102, ACH-3422, and sovaprevir, under the timelines it projects in current and future clinical trials; obtain and maintain necessary regulatory approvals; obtain and maintain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; manage litigation; raise the substantial additional capital needed to achieve its business objectives; and successfully execute on its business strategies.
These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2014, and its subsequent SEC filings.
In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.
ABBVIE PRESENTS LATE-BREAKING, PRELIMINARY PHASE 3B DATA WITH VIEKIRAX® + EXVIERA® IN HCV PATIENTS W-RENAL IMPAIRMENT
ABBVIE PRESENTS LATE-BREAKING, PRELIMINARY PHASE 3B DATA WITH VIEKIRAX® + EXVIERA® IN CHRONIC HEPATITIS C PATIENTS WITH RENAL IMPAIRMENT AT THE INTERNATIONAL LIVER CONGRESS™ 2015
- RUBY-I EVALUATES TREATMENT-NAÏVE, NON-CIRRHOTIC, GENOTYPE 1 CHRONIC HEPATITIS C PATIENTS WITH SEVERE RENAL IMPAIRMENT
- IN PRELIMINARY DATA FROM RUBY-I, PATIENTS RECEIVING VIEKIRAX + EXVIERA WITH OR WITHOUT RIBAVIRIN WHO REACHED POST-TREATMENT WEEK FOUR (N=10 OF 20 ENROLLED) ACHIEVED 100 PERCENT SUSTAINED VIROLOGIC RESPONSE AT FOUR WEEKS POST-TREATMENT (SVR4)1
- ABBVIE'S PHASE 3B STUDIES EXPLORE VIEKIRAX + EXVIERA IN ADDITIONAL PATIENT POPULATIONS SEEN IN CLINICAL PRACTICE AND ACROSS MULTIPLE COUNTRIES AROUND THE WORLD
Apr 25, 2015
VIENNA, April 25, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new, preliminary safety and efficacy data from the first cohort of its ongoing, Phase 3b RUBY-I study. RUBY-I is evaluating VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets) with or without ribavirin (RBV) in treatment-naïve, non-cirrhotic, genotype 1 (GT1) chronic hepatitis C patients with severe renal impairment (stage 4 or 5), including those on hemodialysis. The primary endpoint of the study is the percentage of patients achieving sustained virologic response at 12 weeks post-treatment (SVR12). Patients who reached post-treatment week four to date (n=10 of 20 enrolled) achieved 100 percent SVR4 (n=10/10).1 RUBY-I was presented as a late-breaker today at The International Liver Congress™ (ILC) 2015, the 50th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.
"Treating hepatitis C patients with severe renal impairment may be a concern, particularly in those patients on hemodialysis," said Paul J. Pockros, M.D., director of Liver Disease Center Scripps Clinic and director of clinical research at Scripps Translational Science Institute in La Jolla, California. "With limited data currently available on the safety and efficacy of interferon-free treatments for patients with renal impairment, the preliminary results seen in RUBY-I show promising initial SVR rates with the VIEKIRAX + EXVIERA regimen in a dedicated study for this often difficult-to-treat patient population."
Additionally, RUBY-I data showed no virologic failures to date.1 Preliminary safety analyses reported that patients experienced mainly mild or moderate adverse events when receiving VIEKIRAX + EXVIERA with or without RBV, most commonly (>20 percent) anemia, fatigue, diarrhea, nausea, dizziness and headache.1 To date, eight of 13 genotype 1a (GT1a) patients had a RBV dose interruption.1
"RUBY-I is part of AbbVie's broader Phase 3b program and demonstrates our continued focus on people living with hepatitis C that have specific needs," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Studies in our Phase 3b program will help to further expand our knowledge of the utility of VIEKIRAX + EXVIERA in special populations encountered in clinical practice."
Additional Phase 3b studies from AbbVie presented at ILC 2015 included MALACHITE-I and MALACHITE-II data, and the TOPAZ-I and TOPAZ-II study design. The MALACHITE studies evaluate adult patients with GT1 chronic HCV infection without cirrhosis receiving VIEKIRAX + EXVIERA with or without RBV compared to treatment with telaprevir with pegylated-interferon and RBV, which remains the standard of care in many regions of the world.2,3 The TOPAZ studies will evaluate the effect of SVR12 on long-term outcomes, five years following treatment with VIEKIRAX + EXVIERA with or without RBV in adults with GT1 chronic HCV infection.4
About RUBY-I Study
RUBY-I is an ongoing, multi-center, open-label Phase 3b study with two cohorts that evaluates the safety and efficacy of 12 or 24 weeks of treatment with VIEKIRAX® + EXVIERA® with or without ribavirin, based on sub-genotype in treatment-naïve, adult patients with genotype 1 (GT1) chronic hepatitis C virus infection who have severe renal impairment (pre-dialysis; stage 4 chronic kidney disease) or end-stage renal disease (on hemodialysis; stage 5 chronic kidney disease) with or without compensated cirrhosis.1 Cohort 1 consists of 20 patients without cirrhosis and cohort 2 will evaluate approximately 20 patients with or without compensated cirrhosis. Ribavirin was started at 200mg once daily for all genotype 1a (GT1a)- infected patients and dosed four hours prior to the start of GT1a patients on hemodialysis. Additional study results, including cohort 2, will be disclosed at future scientific congresses.
About VIEKIRAX® + EXVIERA®
VIEKIRAX + EXVIERA is approved in the European Union for the treatment of genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including patients with compensated cirrhosis. VIEKIRAX is approved in the European Union for the treatment of genotype 4 (GT4) chronic HCV infection.
VIEKIRAX consists of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily, and EXVIERA consists of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily taken with or without ribavirin (RBV), dosed twice daily based on patient type. VIEKIRAX + EXVIERA is taken for 12 weeks with or without RBV, except in GT1a and GT4 patients with compensated cirrhosis, who should take it for 24 weeks with RBV.
Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for hepatitis C protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of chronic hepatitis C.
Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.
About AbbVie's HCV Clinical Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating interferon-free, all-oral treatments with or without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's global Phase 3b program plans to include more than 2,800 genotype 1 patients in over 200 study centers worldwide, including the U.S., Canada, Europe, Russia and Brazil. Data in patients with severe renal impairment, including patients on hemodialysis, will be presented at ILC. Additionally, AbbVie's Phase 3b HCV program includes studies in patients with decompensated and compensated cirrhosis. Data from these studies will be presented at future scientific congresses.
Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.
VIEKIRAX® + EXVIERA® EU Indication
VIEKIRAX is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults. EXVIERA is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.
Important EU Safety Information
Contraindications:
VIEKIRAX + EXVIERA are contraindicated in patients with severe hepatic impairment (Child-Pugh C). Patients taking ethinyl estradiol-containing medicinal products must discontinue them and switch to an alternative method of contraception prior to initiating VIEKIRAX + EXVIERA. Do not give VIEKIRAX with certain drugs that are sensitive CYP3A substrates or strong inhibitors of CYP3A. Do not give VIEKIRAX and EXVIERA with strong or moderate enzyme inducers. Do not give EXVIERA with certain drugs that are strong inhibitors of CYP2C8.
Special warnings and precautions for use:
VIEKIRAX and EXVIERA are not recommended as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C infection.
Pregnancy and concomitant use with ribavirin
When VIEKIRAX + EXVIERA are used in combination with ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and 6 months after the treatment. Refer to the Summary of Product Characteristics for ribavirin for additional information.
ALT elevations
Transient elevations of ALT to >5x ULN without concomitant elevations of bilirubin occurred in clinical trials with VIEKIRAX + EXVIERA and were more frequent in a subgroup who were using ethinyl estradiol-containing contraceptives.
Use with concomitant medicinal products
Use caution when administering VIEKIRAX with fluticasone or other glucocorticoids that are metabolized by CYP3A4. A reduction in colchicine dosage or interruption in colchicine is recommended in patients with normal renal or hepatic function. VIEKIRAX with or without EXVIERA is expected to increase exposure of statins so certain statins need to be discontinued or dosages reduced. Low dose ritonavir, which is part of VIEKIRAX, may select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-infected patients without suppressive antiretroviral therapy should not be treated with VIEKIRAX.
Adverse Reactions
Most common (>20 percent) adverse reactions for VIEKIRAX + EXVIERA with RBV were fatigue and nausea.
Full summary of product characteristics is available at www.ema.europa.eu
Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs more than 26,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.
Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.
Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
References:
1 Pockros P, et al. Safety Of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir For Treating HCV GT1 Infection In Patients With Severe Renal Impairment Or End-stage Renal Disease: The RUBY-I Study. Presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria
2 Conway B, et al. MALACHITE-I: Phase 3b Trial Of Ombitasvir/Paritaprevir/R And Dasabuvir +/-Ribavirin Or Telaprevir + Peginterferon/Ribavirin In Treatment-naïve Adults With HCV Genotype 1. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria
3 Dore G, et al. MALACHITE-II: Phase 3b Trial Of Ombitasvir/Paritaprevir/R And Dasabuvir + Ribavirin Or Telaprevir + Peginterferon/Ribavirin In Peginterferon/Ribavirin Treatment-experienced Adults With HCV Genotype 1. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria
4 Dumas E, et al. Phase 3b Studies To Assess Long-term Clinical Outcomes In HCV GT1-infected Patients Treated With Ombitasvir/Paritaprevir/Ritonavir And Dasabuvir With Or Without Ribavirin. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria.
SOURCE AbbVie
For further information: Media, Javier Boix, +1 (847) 937-6113, javier.boix@abbvie.com, or Jackie Finley, +1 (847) 937-3998, jaquelin.finley@abbvie.com, or Investor Relations, Liz Shea, +1 (847) 935-2211, liz.shea@abbvie.com
- RUBY-I EVALUATES TREATMENT-NAÏVE, NON-CIRRHOTIC, GENOTYPE 1 CHRONIC HEPATITIS C PATIENTS WITH SEVERE RENAL IMPAIRMENT
- IN PRELIMINARY DATA FROM RUBY-I, PATIENTS RECEIVING VIEKIRAX + EXVIERA WITH OR WITHOUT RIBAVIRIN WHO REACHED POST-TREATMENT WEEK FOUR (N=10 OF 20 ENROLLED) ACHIEVED 100 PERCENT SUSTAINED VIROLOGIC RESPONSE AT FOUR WEEKS POST-TREATMENT (SVR4)1
- ABBVIE'S PHASE 3B STUDIES EXPLORE VIEKIRAX + EXVIERA IN ADDITIONAL PATIENT POPULATIONS SEEN IN CLINICAL PRACTICE AND ACROSS MULTIPLE COUNTRIES AROUND THE WORLD
Apr 25, 2015
VIENNA, April 25, 2015 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new, preliminary safety and efficacy data from the first cohort of its ongoing, Phase 3b RUBY-I study. RUBY-I is evaluating VIEKIRAX® (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA® (dasabuvir tablets) with or without ribavirin (RBV) in treatment-naïve, non-cirrhotic, genotype 1 (GT1) chronic hepatitis C patients with severe renal impairment (stage 4 or 5), including those on hemodialysis. The primary endpoint of the study is the percentage of patients achieving sustained virologic response at 12 weeks post-treatment (SVR12). Patients who reached post-treatment week four to date (n=10 of 20 enrolled) achieved 100 percent SVR4 (n=10/10).1 RUBY-I was presented as a late-breaker today at The International Liver Congress™ (ILC) 2015, the 50th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria.
"Treating hepatitis C patients with severe renal impairment may be a concern, particularly in those patients on hemodialysis," said Paul J. Pockros, M.D., director of Liver Disease Center Scripps Clinic and director of clinical research at Scripps Translational Science Institute in La Jolla, California. "With limited data currently available on the safety and efficacy of interferon-free treatments for patients with renal impairment, the preliminary results seen in RUBY-I show promising initial SVR rates with the VIEKIRAX + EXVIERA regimen in a dedicated study for this often difficult-to-treat patient population."
Additionally, RUBY-I data showed no virologic failures to date.1 Preliminary safety analyses reported that patients experienced mainly mild or moderate adverse events when receiving VIEKIRAX + EXVIERA with or without RBV, most commonly (>20 percent) anemia, fatigue, diarrhea, nausea, dizziness and headache.1 To date, eight of 13 genotype 1a (GT1a) patients had a RBV dose interruption.1
"RUBY-I is part of AbbVie's broader Phase 3b program and demonstrates our continued focus on people living with hepatitis C that have specific needs," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Studies in our Phase 3b program will help to further expand our knowledge of the utility of VIEKIRAX + EXVIERA in special populations encountered in clinical practice."
Additional Phase 3b studies from AbbVie presented at ILC 2015 included MALACHITE-I and MALACHITE-II data, and the TOPAZ-I and TOPAZ-II study design. The MALACHITE studies evaluate adult patients with GT1 chronic HCV infection without cirrhosis receiving VIEKIRAX + EXVIERA with or without RBV compared to treatment with telaprevir with pegylated-interferon and RBV, which remains the standard of care in many regions of the world.2,3 The TOPAZ studies will evaluate the effect of SVR12 on long-term outcomes, five years following treatment with VIEKIRAX + EXVIERA with or without RBV in adults with GT1 chronic HCV infection.4
About RUBY-I Study
RUBY-I is an ongoing, multi-center, open-label Phase 3b study with two cohorts that evaluates the safety and efficacy of 12 or 24 weeks of treatment with VIEKIRAX® + EXVIERA® with or without ribavirin, based on sub-genotype in treatment-naïve, adult patients with genotype 1 (GT1) chronic hepatitis C virus infection who have severe renal impairment (pre-dialysis; stage 4 chronic kidney disease) or end-stage renal disease (on hemodialysis; stage 5 chronic kidney disease) with or without compensated cirrhosis.1 Cohort 1 consists of 20 patients without cirrhosis and cohort 2 will evaluate approximately 20 patients with or without compensated cirrhosis. Ribavirin was started at 200mg once daily for all genotype 1a (GT1a)- infected patients and dosed four hours prior to the start of GT1a patients on hemodialysis. Additional study results, including cohort 2, will be disclosed at future scientific congresses.
About VIEKIRAX® + EXVIERA®
VIEKIRAX + EXVIERA is approved in the European Union for the treatment of genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including patients with compensated cirrhosis. VIEKIRAX is approved in the European Union for the treatment of genotype 4 (GT4) chronic HCV infection.
VIEKIRAX consists of the fixed-dose combination of paritaprevir 150mg (NS3/4A protease inhibitor) and ritonavir 100mg with ombitasvir 25mg (NS5A inhibitor), dosed once daily, and EXVIERA consists of dasabuvir 250mg (non-nucleoside NS5B polymerase inhibitor) dosed twice daily taken with or without ribavirin (RBV), dosed twice daily based on patient type. VIEKIRAX + EXVIERA is taken for 12 weeks with or without RBV, except in GT1a and GT4 patients with compensated cirrhosis, who should take it for 24 weeks with RBV.
Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for hepatitis C protease inhibitors and regimens that include protease inhibitors. Paritaprevir has been developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of chronic hepatitis C.
Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.
About AbbVie's HCV Clinical Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating interferon-free, all-oral treatments with or without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's global Phase 3b program plans to include more than 2,800 genotype 1 patients in over 200 study centers worldwide, including the U.S., Canada, Europe, Russia and Brazil. Data in patients with severe renal impairment, including patients on hemodialysis, will be presented at ILC. Additionally, AbbVie's Phase 3b HCV program includes studies in patients with decompensated and compensated cirrhosis. Data from these studies will be presented at future scientific congresses.
Additional information about AbbVie's hepatitis C development program can be found on www.clinicaltrials.gov.
VIEKIRAX® + EXVIERA® EU Indication
VIEKIRAX is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults. EXVIERA is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adults.
Important EU Safety Information
Contraindications:
VIEKIRAX + EXVIERA are contraindicated in patients with severe hepatic impairment (Child-Pugh C). Patients taking ethinyl estradiol-containing medicinal products must discontinue them and switch to an alternative method of contraception prior to initiating VIEKIRAX + EXVIERA. Do not give VIEKIRAX with certain drugs that are sensitive CYP3A substrates or strong inhibitors of CYP3A. Do not give VIEKIRAX and EXVIERA with strong or moderate enzyme inducers. Do not give EXVIERA with certain drugs that are strong inhibitors of CYP2C8.
Special warnings and precautions for use:
VIEKIRAX and EXVIERA are not recommended as monotherapy and should be used in combination with other medicinal products for the treatment of hepatitis C infection.
Pregnancy and concomitant use with ribavirin
When VIEKIRAX + EXVIERA are used in combination with ribavirin, women of childbearing potential or their male partners must use an effective form of contraception during the treatment and 6 months after the treatment. Refer to the Summary of Product Characteristics for ribavirin for additional information.
ALT elevations
Transient elevations of ALT to >5x ULN without concomitant elevations of bilirubin occurred in clinical trials with VIEKIRAX + EXVIERA and were more frequent in a subgroup who were using ethinyl estradiol-containing contraceptives.
Use with concomitant medicinal products
Use caution when administering VIEKIRAX with fluticasone or other glucocorticoids that are metabolized by CYP3A4. A reduction in colchicine dosage or interruption in colchicine is recommended in patients with normal renal or hepatic function. VIEKIRAX with or without EXVIERA is expected to increase exposure of statins so certain statins need to be discontinued or dosages reduced. Low dose ritonavir, which is part of VIEKIRAX, may select for PI resistance in HIV co-infected patients without ongoing antiretroviral therapy. HIV co-infected patients without suppressive antiretroviral therapy should not be treated with VIEKIRAX.
Adverse Reactions
Most common (>20 percent) adverse reactions for VIEKIRAX + EXVIERA with RBV were fatigue and nausea.
Full summary of product characteristics is available at www.ema.europa.eu
Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs more than 26,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.
Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.
Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
References:
1 Pockros P, et al. Safety Of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir For Treating HCV GT1 Infection In Patients With Severe Renal Impairment Or End-stage Renal Disease: The RUBY-I Study. Presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria
2 Conway B, et al. MALACHITE-I: Phase 3b Trial Of Ombitasvir/Paritaprevir/R And Dasabuvir +/-Ribavirin Or Telaprevir + Peginterferon/Ribavirin In Treatment-naïve Adults With HCV Genotype 1. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria
3 Dore G, et al. MALACHITE-II: Phase 3b Trial Of Ombitasvir/Paritaprevir/R And Dasabuvir + Ribavirin Or Telaprevir + Peginterferon/Ribavirin In Peginterferon/Ribavirin Treatment-experienced Adults With HCV Genotype 1. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria
4 Dumas E, et al. Phase 3b Studies To Assess Long-term Clinical Outcomes In HCV GT1-infected Patients Treated With Ombitasvir/Paritaprevir/Ritonavir And Dasabuvir With Or Without Ribavirin. Abstract presented at the 50th International Liver Congress (ILC); April 22-26; Vienna, Austria.
SOURCE AbbVie
For further information: Media, Javier Boix, +1 (847) 937-6113, javier.boix@abbvie.com, or Jackie Finley, +1 (847) 937-3998, jaquelin.finley@abbvie.com, or Investor Relations, Liz Shea, +1 (847) 935-2211, liz.shea@abbvie.com
Geno 2-5: Gilead Results of Sofosbuvir-Based Regimens in Chronic Hepatitis C Patients
Gilead Announces Results From Studies Evaluating Sofosbuvir-Based Regimens in Chronic Hepatitis C Patients With Genotypes 2-5
-- High Cure Rates Observed Across a Range of Genotypes --
VIENNA, Austria--(BUSINESS WIRE)--Apr. 25, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two studies evaluating the safety and efficacy of investigational uses of sofosbuvir-based regimens in chronic hepatitis C virus (HCV)-infected patients with genotypes 2, 3, 4 and 5. Results from the BOSON study of Sovaldi® (sofosbuvir 400 mg) in combination with ribavirin (RBV) or with pegylated interferon (PEG)/RBV demonstrated high cure rates across all patients with genotypes 2 and 3. Separately, results from a Phase 2 study demonstrate the safety and efficacy of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) in patients with genotypes 4 or 5 infection. Data from both studies will be presented in oral sessions at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria.
Sovaldi and Harvoni are each approved in the United States for the treatment of chronic HCV infection. Sovaldi is used in combination with other agents and its efficacy has been established in patients with genotypes 1-4; Harvoni is indicated for patients with genotype 1.
BOSON (Study GS-US-334-0153, #LB05), a randomized Phase 3 study of 592 patients, evaluated the safety and efficacy of Sovaldi plus RBV for 16 or 24 weeks compared with Sovaldi plus PEG/RBV for 12 weeks among treatment-naïve or treatment-experienced genotype 3 patients with and without cirrhosis and treatment-experienced genotype 2 patients with cirrhosis. Thirty-seven percent of study participants had cirrhosis.
Among genotype 3 patients, rates of sustained virologic response 12 weeks after treatment (SVR12) were highest among those receiving Sovaldi plus PEG/RBV for 12 weeks (93 percent, n=168/181), compared to those receiving Sovaldi plus RBV for 24 weeks (84 percent, n=153/182) or for 16 weeks (71 percent, n=128/181). Treatment-experienced genotype 3 patients with cirrhosis receiving Sovaldi plus PEG/RBV demonstrated SVR12 rates of 86 percent (30/35).
Genotype 2 patients also demonstrated high SVR12 rates across all treatment arms. SVR12 rates among patients receiving Sovaldi plus PEG/RBV were 94 percent (15/16), and 100 percent (17/17) and 87 percent (13/15) for those receiving Sovaldi plus RBV for 24 and 16 weeks, respectively.
Sovaldi plus PEG/RBV and Sovaldi plus RBV were well tolerated. The most common adverse events in the study were fatigue, headache, insomnia and nausea. Overall, six patients (1 percent) discontinued treatment due to adverse events, one of whom was treated with Sovaldi plus PEG/RBV.
“It remains difficult to achieve a virological response in genotype 3, which is one of the most prevalent genotypes in the world, with higher prevalence in Europe and Asia,” said Graham R. Foster, FRCP, PhD, Professor of Hepatology, The Liver Unit, Queen Mary's University of London, Barts Health, London, United Kingdom. “These results are compelling because they represent the highest cure rates observed among treatment-experienced, cirrhotic genotype 3 patients in any Phase 3 clinical trial to date.”
In a separate open-label Phase 2 study of Harvoni conducted in France (Study GS-US-337-1119, O056), results demonstrated high SVR rates in both treatment-naïve and treatment-experienced patients with chronic HCV genotypes 4 or 5 infection, 50 percent of whom had cirrhosis.
Ninety-three percent of patients with genotype 4 (41/44) and 95 percent of patients with genotype 5 (39/41) achieved SVR12. Response rates were similar among both treatment-naïve and -experienced patients and regardless of cirrhosis.
The most common adverse events (affecting more than 10 percent of patients) were asthenia, headache and fatigue. Most adverse events were mild or moderate in severity and none resulted in treatment discontinuation. There were no grade 3 or 4 clinical laboratory abnormalities.
“HCV genotype 4 and 5 are less prevalent than other genotypes and therefore, have traditionally not been closely studied,” said Armand Abergel, MD, PhD, Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire-Estaing, Université d'Auvergne, Clermont-Ferrand, France. “These data provide important evidence that the all-oral, ribavirin-free Harvoni regimen is both safe and effective for many patients with genotype 4 or 5, regardless of prior treatment experience.”
The safety and efficacy of these investigational uses of Harvoni and Sovaldi have not been established.
Important Safety Information About Sovaldi
Contraindications
Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications.
Warnings and Precautions
Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral (DAA): Amiodarone is not recommended for use with Sovaldi in combination with another DAA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
Pregnancy: Use with ribavirin or peginterferon alfa/ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin.
Use with Potent P-gp Inducers: Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.
Adverse Reactions
Most common (≥20 percent, all grades) adverse reactions for:
Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia
Sovaldi + ribavirin combination therapy were fatigue, and headache
Drug Interactions
In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.
Important Safety Information About Harvoni
Warnings and Precautions
Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).
Adverse Reactions
Most common (≥10 percent, all grades) adverse reactions were fatigue and headache.
Drug Interactions
In addition to rifampin and St. John’s wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.
Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.
Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.
About Gilead
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.
Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may observe unfavorable results from additional clinical trials involving Sovaldi and Harvoni for various patient populations, including those with genotype 2, 3, 4 and 5 HCV. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full Prescribing Information for Sovaldi and Harvoni is available at www.gilead.com.
Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc., or its related companies.
For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
-- High Cure Rates Observed Across a Range of Genotypes --
VIENNA, Austria--(BUSINESS WIRE)--Apr. 25, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two studies evaluating the safety and efficacy of investigational uses of sofosbuvir-based regimens in chronic hepatitis C virus (HCV)-infected patients with genotypes 2, 3, 4 and 5. Results from the BOSON study of Sovaldi® (sofosbuvir 400 mg) in combination with ribavirin (RBV) or with pegylated interferon (PEG)/RBV demonstrated high cure rates across all patients with genotypes 2 and 3. Separately, results from a Phase 2 study demonstrate the safety and efficacy of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) in patients with genotypes 4 or 5 infection. Data from both studies will be presented in oral sessions at the 50th Annual Meeting of the European Association for the Study of the Liver (The International Liver Congress™ 2015) in Vienna, Austria.
Sovaldi and Harvoni are each approved in the United States for the treatment of chronic HCV infection. Sovaldi is used in combination with other agents and its efficacy has been established in patients with genotypes 1-4; Harvoni is indicated for patients with genotype 1.
BOSON (Study GS-US-334-0153, #LB05), a randomized Phase 3 study of 592 patients, evaluated the safety and efficacy of Sovaldi plus RBV for 16 or 24 weeks compared with Sovaldi plus PEG/RBV for 12 weeks among treatment-naïve or treatment-experienced genotype 3 patients with and without cirrhosis and treatment-experienced genotype 2 patients with cirrhosis. Thirty-seven percent of study participants had cirrhosis.
Among genotype 3 patients, rates of sustained virologic response 12 weeks after treatment (SVR12) were highest among those receiving Sovaldi plus PEG/RBV for 12 weeks (93 percent, n=168/181), compared to those receiving Sovaldi plus RBV for 24 weeks (84 percent, n=153/182) or for 16 weeks (71 percent, n=128/181). Treatment-experienced genotype 3 patients with cirrhosis receiving Sovaldi plus PEG/RBV demonstrated SVR12 rates of 86 percent (30/35).
Genotype 2 patients also demonstrated high SVR12 rates across all treatment arms. SVR12 rates among patients receiving Sovaldi plus PEG/RBV were 94 percent (15/16), and 100 percent (17/17) and 87 percent (13/15) for those receiving Sovaldi plus RBV for 24 and 16 weeks, respectively.
Sovaldi plus PEG/RBV and Sovaldi plus RBV were well tolerated. The most common adverse events in the study were fatigue, headache, insomnia and nausea. Overall, six patients (1 percent) discontinued treatment due to adverse events, one of whom was treated with Sovaldi plus PEG/RBV.
“It remains difficult to achieve a virological response in genotype 3, which is one of the most prevalent genotypes in the world, with higher prevalence in Europe and Asia,” said Graham R. Foster, FRCP, PhD, Professor of Hepatology, The Liver Unit, Queen Mary's University of London, Barts Health, London, United Kingdom. “These results are compelling because they represent the highest cure rates observed among treatment-experienced, cirrhotic genotype 3 patients in any Phase 3 clinical trial to date.”
In a separate open-label Phase 2 study of Harvoni conducted in France (Study GS-US-337-1119, O056), results demonstrated high SVR rates in both treatment-naïve and treatment-experienced patients with chronic HCV genotypes 4 or 5 infection, 50 percent of whom had cirrhosis.
Ninety-three percent of patients with genotype 4 (41/44) and 95 percent of patients with genotype 5 (39/41) achieved SVR12. Response rates were similar among both treatment-naïve and -experienced patients and regardless of cirrhosis.
The most common adverse events (affecting more than 10 percent of patients) were asthenia, headache and fatigue. Most adverse events were mild or moderate in severity and none resulted in treatment discontinuation. There were no grade 3 or 4 clinical laboratory abnormalities.
“HCV genotype 4 and 5 are less prevalent than other genotypes and therefore, have traditionally not been closely studied,” said Armand Abergel, MD, PhD, Department of Hepatology and Gastroenterology, Centre Hospitalier Universitaire-Estaing, Université d'Auvergne, Clermont-Ferrand, France. “These data provide important evidence that the all-oral, ribavirin-free Harvoni regimen is both safe and effective for many patients with genotype 4 or 5, regardless of prior treatment experience.”
The safety and efficacy of these investigational uses of Harvoni and Sovaldi have not been established.
Important Safety Information About Sovaldi
Contraindications
Sovaldi combination treatment with ribavirin or with peginterferon alfa plus ribavirin is contraindicated in women who are pregnant or may become pregnant and men whose female partners are pregnant because of the risk for birth defects and fetal death associated with ribavirin. Contraindications to peginterferon alfa and ribavirin also apply to Sovaldi combination treatment. Refer to the prescribing information of peginterferon alfa and ribavirin for a list of their contraindications.
Warnings and Precautions
Serious Symptomatic Bradycardia When Coadministered with Amiodarone and Another HCV Direct Acting Antiviral (DAA): Amiodarone is not recommended for use with Sovaldi in combination with another DAA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
Pregnancy: Use with ribavirin or peginterferon alfa/ribavirin: Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Female patients of childbearing potential and their male partners must use two forms of non-hormonal contraception during treatment and for at least 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. Refer to the prescribing information for ribavirin.
Use with Potent P-gp Inducers: Rifampin and St. John’s wort should not be used with Sovaldi as they may significantly decrease sofosbuvir plasma concentration, reducing its therapeutic effect.
Adverse Reactions
Most common (≥20 percent, all grades) adverse reactions for:
Sovaldi + peginterferon alfa + ribavirin combination therapy were fatigue, headache, nausea, insomnia, and anemia
Sovaldi + ribavirin combination therapy were fatigue, and headache
Drug Interactions
In addition to rifampin and St. John’s wort, coadministration of Sovaldi is not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of sofosbuvir, reducing its therapeutic effect.
Important Safety Information About Harvoni
Warnings and Precautions
Risk of Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Harvoni due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.
Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).
Adverse Reactions
Most common (≥10 percent, all grades) adverse reactions were fatigue and headache.
Drug Interactions
In addition to rifampin and St. John’s wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.
Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.
Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.
About Gilead
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.
Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the risk that Gilead may observe unfavorable results from additional clinical trials involving Sovaldi and Harvoni for various patient populations, including those with genotype 2, 3, 4 and 5 HCV. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. full Prescribing Information for Sovaldi and Harvoni is available at www.gilead.com.
Sovaldi and Harvoni are registered trademarks of Gilead Sciences, Inc., or its related companies.
For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
BMS announces 12-week HCV regimen of daclatasvir and sofosbuvir at EASL
ALLY-1 Trial Results Show Investigational Daclatasvir-Based Regimen Cures 94% of Post-Liver Transplant Patients with Hepatitis C and Up to 94% of Hepatitis C Patients with Cirrhosis (Child-Pugh Class A or B)
97% of post-transplant patients with HCV genotype 1a achieved cure
91% of post-transplant patients with HCV genotype 3 achieved cure
No need seen to alter existing transplantation medication regimens
Saturday, April 25, 2015 10:00 am EDT
(PRINCETON, N.J., APRIL 25, 2015) – Bristol-Myers Squibb Company (NYSE:BMY) today announced that primary endpoints were successfully met in ALLY-1, a Phase III clinical trial evaluating a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) with either advanced cirrhosis or post-liver transplant recurrence of HCV. The data was presented as a late-breaker at The International Liver Congress™ 2015, the 50th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria from April 22-26.
“The results of the ALLY-1 trial point to the potential of this investigational daclatasvir-based regimen in a patient population with high unmet needs despite recent advances in hepatitis C treatment,” said Fred Poordad, M.D., ALLY-1 Lead Investigator and Clinical Professor of Medicine at The University of Texas Health Science Center at San Antonio. “Transplant patients take a variety of immunosuppressive medications to prevent organ rejection; that complicates the treatment of hepatitis C. In ALLY-1, we saw no drug-drug interactions between transplant and hepatitis C therapies and no need to make dose adjustments to patients’ transplant-related drugs while they received the daclatasvir-based regimen that resulted in high SVR12 rates.”
The study’s primary endpoints were reached, with 95% of post-transplant genotype 1 patients and 82% of genotype 1 patients with advanced cirrhosis achieving SVR12. Among all ALLY-1 patients, 94% of those with post-transplant HCV recurrence and 83% of all participants with advanced cirrhosis achieved cure (sustained virologic response 12 weeks after treatment; SVR12).
The Child-Pugh scoring system is commonly used to assess the severity and prognosis of chronic liver disease and cirrhosis, and uses an A through C classification (C being the most advanced) to categorize disease progression. Patients with class C cirrhosis are decompensated, often with later-stage conditions such as ascites (the build-up of fluid in the abdomen), hepatic encephalopathy (confusion or altered level of consciousness due to the liver’s inability to remove toxins from the blood), and abnormal liver function, which can complicate treatment. The ALLY-1 trial included 16 patients with decompensated cirrhosis Child-Pugh class C; nine (56%) achieved SVR12.
Over the course of the study, four advanced cirrhotic patients received a liver transplant during treatment; 3 of 4 extended treatment post-transplant (see study design below), and all 4 achieved SVR12.
In the study, there were no serious adverse events related to study medications throughout the treatment phase. The most common adverse events (≥10%) were headache (15%, 36%), fatigue (18%, 28%), anemia (20%, 19%), diarrhea (8%, 19%), nausea (17%, 6%), and arthralgia (2%, 13%) in the advanced cirrhotic and post-transplant cohorts, respectively. One patient discontinued therapy after 31 days due to headache, but still achieved SVR12. Nine patients in the cirrhosis cohort relapsed post-treatment, and one had detectable HCV RNA at the end of treatment; there were no on-treatment virologic breakthroughs. Three patients (genotypes 1a, 1b, 3) in the post-transplantation cohort relapsed. All 12 patients with relapse are being retreated with daclatasvir and sofosbuvir with ribavirin for 24 weeks.
HCV is the leading indication for liver transplantation worldwide. Without treatment, HCV infection of the new liver after transplant is inevitable, and is associated with rapid progression to cirrhosis and death in up to 30% of patients within 5 years. The ALLY-1 study is the third study to report out of the Phase III ALLY program, which evaluates daclatasvir in combination with sofosbuvir in multiple high-unmet need patient populations and is at the center of Bristol-Myers Squibb’s HCV research focus. The ALLY-2 and ALLY-3 studies have previously been presented at the 2015 Conference for Retroviral and Opportunistic Infections and the 2014 American Association for the Study of the Liver’s The Liver Meeting, respectively, and subanalyses from each study with the ribavirin-free regimen of daclatasvir and sofosbuvir were presented as posters during EASL 2015.
Additionally, EASL issued 2015 Hepatitis C treatment guidelines that include a regimen of daclatasvir+sofosbuvir as the first 12-week treatment for patients with genotype-3 virus. The EASL guidelines now list daclatasvir+sofosbuvir regimens as options for treating all HCV genotypes and for use with patients coinfected with HCV/HIV. (Guidelines available here.)
Other Bristol-Myers Squibb presentations at The International Liver Congress included data from compassionate use programs in the EU that add to the real-world clinical evidence informing the use of daclatasvir-based regimens to treat patients with HCV conditions posing high unmet medical needs.
“The ALLY-1 trial results build off the ALLY-2 and ALLY-3 studies by demonstrating the versatility of the daclatasvir-based regimen to provide HCV cure in multiple patient populations that have been historically hard to manage, such as HCV genotype 3 patients, HIV/HCV coinfected patients, and patients with decompensated cirrhosis,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “Post-liver transplant and cirrhotic patients represent a still-unmet need and continue to present challenges to currently available regimens.”
About ALLY-1: Study Design
This Phase III open-label clinical trial enrolled treatment-naïve and treatment-experienced patients with HCV infection of any genotype in 2 cohorts: advanced cirrhosis (n=60) and post-liver transplant with HCV recurrence (n=53). All patients received daclatasvir 60 mg plus sofosbuvir 400 mg once-daily with ribavirin initially dosed at 600 mg/d (with potential for adjustment based on hemoglobin levels and creatinine clearance) for 12 weeks. Patients receiving a variety of immunosuppressive agents were permitted. In the cirrhosis cohort, patients transplanted during treatment could receive 12 weeks of extended treatment immediately post-transplant, regardless of treatment duration before transplant. The primary endpoint was the SVR12 rate (defined as HCV RNA <LLOQ (25 IU/mL) at post-treatment week 12) among genotype 1 patients in each cohort.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 20 percent may progress to liver cancer.
About Bristol-Myers Squibb’s HCV Portfolio
Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, a NS5A complex inhibitor which continues to be investigated in multiple treatment regimens and in patients with co-morbidities.
Daclatasvir was approved in Europe in August 2014 for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Beyond Europe, it is approved in Japan, as well as multiple countries in Latin and South America, the Middle East and Asia Pacific. Additionally, the U.S. FDA currently is reviewing a New Drug Application (NDA) for the use of daclatasvir and sofosbuvir to treat patients with HCV genotype 3.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that daclatasvir will receive regulatory approval in the United States, or if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2014, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
Contact:
Media:
Robert Perry, Office: 609-419-5378, Cell: 407-492-4616, rob.perry@bms.com
Investors:
Ranya Dajani, 609-252-5330, ranya.dajani@bms.com
97% of post-transplant patients with HCV genotype 1a achieved cure
91% of post-transplant patients with HCV genotype 3 achieved cure
No need seen to alter existing transplantation medication regimens
Saturday, April 25, 2015 10:00 am EDT
(PRINCETON, N.J., APRIL 25, 2015) – Bristol-Myers Squibb Company (NYSE:BMY) today announced that primary endpoints were successfully met in ALLY-1, a Phase III clinical trial evaluating a 12-week regimen of daclatasvir and sofosbuvir once-daily with ribavirin for the treatment of patients with chronic hepatitis C virus (HCV) with either advanced cirrhosis or post-liver transplant recurrence of HCV. The data was presented as a late-breaker at The International Liver Congress™ 2015, the 50th annual meeting of the European Association for the Study of the Liver (EASL) in Vienna, Austria from April 22-26.
“The results of the ALLY-1 trial point to the potential of this investigational daclatasvir-based regimen in a patient population with high unmet needs despite recent advances in hepatitis C treatment,” said Fred Poordad, M.D., ALLY-1 Lead Investigator and Clinical Professor of Medicine at The University of Texas Health Science Center at San Antonio. “Transplant patients take a variety of immunosuppressive medications to prevent organ rejection; that complicates the treatment of hepatitis C. In ALLY-1, we saw no drug-drug interactions between transplant and hepatitis C therapies and no need to make dose adjustments to patients’ transplant-related drugs while they received the daclatasvir-based regimen that resulted in high SVR12 rates.”
The study’s primary endpoints were reached, with 95% of post-transplant genotype 1 patients and 82% of genotype 1 patients with advanced cirrhosis achieving SVR12. Among all ALLY-1 patients, 94% of those with post-transplant HCV recurrence and 83% of all participants with advanced cirrhosis achieved cure (sustained virologic response 12 weeks after treatment; SVR12).
The Child-Pugh scoring system is commonly used to assess the severity and prognosis of chronic liver disease and cirrhosis, and uses an A through C classification (C being the most advanced) to categorize disease progression. Patients with class C cirrhosis are decompensated, often with later-stage conditions such as ascites (the build-up of fluid in the abdomen), hepatic encephalopathy (confusion or altered level of consciousness due to the liver’s inability to remove toxins from the blood), and abnormal liver function, which can complicate treatment. The ALLY-1 trial included 16 patients with decompensated cirrhosis Child-Pugh class C; nine (56%) achieved SVR12.
Over the course of the study, four advanced cirrhotic patients received a liver transplant during treatment; 3 of 4 extended treatment post-transplant (see study design below), and all 4 achieved SVR12.
In the study, there were no serious adverse events related to study medications throughout the treatment phase. The most common adverse events (≥10%) were headache (15%, 36%), fatigue (18%, 28%), anemia (20%, 19%), diarrhea (8%, 19%), nausea (17%, 6%), and arthralgia (2%, 13%) in the advanced cirrhotic and post-transplant cohorts, respectively. One patient discontinued therapy after 31 days due to headache, but still achieved SVR12. Nine patients in the cirrhosis cohort relapsed post-treatment, and one had detectable HCV RNA at the end of treatment; there were no on-treatment virologic breakthroughs. Three patients (genotypes 1a, 1b, 3) in the post-transplantation cohort relapsed. All 12 patients with relapse are being retreated with daclatasvir and sofosbuvir with ribavirin for 24 weeks.
HCV is the leading indication for liver transplantation worldwide. Without treatment, HCV infection of the new liver after transplant is inevitable, and is associated with rapid progression to cirrhosis and death in up to 30% of patients within 5 years. The ALLY-1 study is the third study to report out of the Phase III ALLY program, which evaluates daclatasvir in combination with sofosbuvir in multiple high-unmet need patient populations and is at the center of Bristol-Myers Squibb’s HCV research focus. The ALLY-2 and ALLY-3 studies have previously been presented at the 2015 Conference for Retroviral and Opportunistic Infections and the 2014 American Association for the Study of the Liver’s The Liver Meeting, respectively, and subanalyses from each study with the ribavirin-free regimen of daclatasvir and sofosbuvir were presented as posters during EASL 2015.
Additionally, EASL issued 2015 Hepatitis C treatment guidelines that include a regimen of daclatasvir+sofosbuvir as the first 12-week treatment for patients with genotype-3 virus. The EASL guidelines now list daclatasvir+sofosbuvir regimens as options for treating all HCV genotypes and for use with patients coinfected with HCV/HIV. (Guidelines available here.)
Other Bristol-Myers Squibb presentations at The International Liver Congress included data from compassionate use programs in the EU that add to the real-world clinical evidence informing the use of daclatasvir-based regimens to treat patients with HCV conditions posing high unmet medical needs.
“The ALLY-1 trial results build off the ALLY-2 and ALLY-3 studies by demonstrating the versatility of the daclatasvir-based regimen to provide HCV cure in multiple patient populations that have been historically hard to manage, such as HCV genotype 3 patients, HIV/HCV coinfected patients, and patients with decompensated cirrhosis,” said Douglas Manion, M.D., Head of Specialty Development, Bristol-Myers Squibb. “Post-liver transplant and cirrhotic patients represent a still-unmet need and continue to present challenges to currently available regimens.”
About ALLY-1: Study Design
This Phase III open-label clinical trial enrolled treatment-naïve and treatment-experienced patients with HCV infection of any genotype in 2 cohorts: advanced cirrhosis (n=60) and post-liver transplant with HCV recurrence (n=53). All patients received daclatasvir 60 mg plus sofosbuvir 400 mg once-daily with ribavirin initially dosed at 600 mg/d (with potential for adjustment based on hemoglobin levels and creatinine clearance) for 12 weeks. Patients receiving a variety of immunosuppressive agents were permitted. In the cirrhosis cohort, patients transplanted during treatment could receive 12 weeks of extended treatment immediately post-transplant, regardless of treatment duration before transplant. The primary endpoint was the SVR12 rate (defined as HCV RNA <LLOQ (25 IU/mL) at post-treatment week 12) among genotype 1 patients in each cohort.
About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. Approximately 170 million people worldwide are infected with hepatitis C. Up to 90 percent of those infected with hepatitis C will not spontaneously clear the virus and will become chronically infected. According to the World Health Organization, up to 20 percent of people with chronic hepatitis C will develop cirrhosis; of those, up to 20 percent may progress to liver cancer.
About Bristol-Myers Squibb’s HCV Portfolio
Bristol-Myers Squibb’s research efforts are focused on advancing late-stage compounds to deliver the most value to patients with hepatitis C. At the core of our pipeline is daclatasvir, a NS5A complex inhibitor which continues to be investigated in multiple treatment regimens and in patients with co-morbidities.
Daclatasvir was approved in Europe in August 2014 for use in combination with other medicinal products across genotypes 1, 2, 3 and 4 for the treatment of chronic hepatitis C virus (HCV) infection in adults. Beyond Europe, it is approved in Japan, as well as multiple countries in Latin and South America, the Middle East and Asia Pacific. Additionally, the U.S. FDA currently is reviewing a New Drug Application (NDA) for the use of daclatasvir and sofosbuvir to treat patients with HCV genotype 3.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward Looking Statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that daclatasvir will receive regulatory approval in the United States, or if approved, that it will become a commercially successful product. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2014, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.
Contact:
Media:
Robert Perry, Office: 609-419-5378, Cell: 407-492-4616, rob.perry@bms.com
Investors:
Ranya Dajani, 609-252-5330, ranya.dajani@bms.com
Subscribe to:
Posts (Atom)