Showing posts with label Simeprevir. Show all posts
Showing posts with label Simeprevir. Show all posts

Thursday, May 24, 2018

Hepatitis C Virus Infection Treatments to Be Discontinued:Technivie, Viekira XR and Simeprevir

In Case You Missed It

FDA Website:
https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm?panels=0&#tabs-4

Also discontinued:

Janssen Pharmaceuticals (New 05/23/2018)
Simeprevir Capsules
Status: Discontinuation

Viekira XR

Abbvie (New 05/22/2018)
Dasabuvir Sodium; Ombitasvir; Paritaprevir; Ritonavir (Viekira XR) Tablets
Status: Discontinuation
Estimated product availability until January 1, 2019.
The product discontinuation is voluntary and not related to product quality, safety or efficacy.

Technivie
Abbvie (New 05/22/2018)
Ombitasvir; Paritaprevir; Ritonavir (Technivie) Tablets
Status: Discontinuation
Estimated product availability until January 1, 2019. The product discontinuation is voluntary and not related to product quality, safety or efficacy.

Article:
MPR > News > Two Hepatitis C Virus Infection Treatments to Be Discontinued
Da Hee Han, PharmD
May 24, 2018
Two Hepatitis C Virus Infection Treatments to Be Discontinued
Two hepatitis C virus (HCV) combination treatments, Technivie (ombitasvir, paritaprevir, ritonavir) and Viekira XR (dasabuvir sodium, ombitasvir, paritaprevir, ritonavir), have been discontinued by AbbVie, according to the Food and Drug Administration (FDA). The discontinuation is voluntary and is not related to product quality, safety or efficacy.
Read the article: https://www.empr.com/news/technivie-viekira-xr-discontinued-hepatitis-c-virus-treatments/article/768368/

Friday, May 26, 2017

Sofosbuvir-Daclatasvir-Simeprevir Plus Ribavirin in Direct-Acting Antiviral–Experienced Patients With Hepatitis C

Clin Infect Dis (2017) 64 (11): 1615-1618.
DOI:

Sofosbuvir-Daclatasvir-Simeprevir Plus Ribavirin in Direct-Acting Antiviral–Experienced Patients With Hepatitis C
Christophe Hézode Slim Fourati Stéphane Chevaliez Giovanna Scoazec Alexandre Soulier Anne Varaut Murielle François Isaac Ruiz Françoise Roudot-Thoraval Ariane Mallat Jean-Michel Pawlotsky

Abstract

We assessed the broadly used, off-label combination of sofosbuvir, daclatasvir, simeprevir, and ribavirin in direct-acting antiviral–experienced patients, as recommended in current guidelines despite scarce data. After 24 weeks’ treatment, sustained virological response 12 weeks after the end of treatment was achieved in 6 patients (60%). Two cirrhotic patients relapsed and 2 discontinued treatment due to serious adverse events.

View Article
PDF Download

Full Text Article
Article link provided by Henry E. Chang.
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

Monday, March 16, 2015

Medivir: New Data on Simeprevir Presented at the Conference of the Asian Pacific Association for the Study of the Liver

Medivir: New Data on Simeprevir Presented at the Conference of the Asian Pacific Association for the Study of the Liver

March 16, 2015 03:41 AM Eastern Daylight Time

STOCKHOLM--(BUSINESS WIRE)--Regulatory News:

“Efficacy safety and pharmacokinetics of 12 weeks of simeprevir in combination with TMC647055 ritonavir and JNJ-56914845 in genotype 1 hepatitis C virus infected patients”

Medivir AB (Nasdaq Stockholm: MVIR) today announced that new clinical data for the once-daily HCV protease inhibitor simeprevir have been presented at the 24th Conference of the Asian Pacific Association for the Study of the Liver (APASL) in Istanbul, Turkey. Six oral and poster presentations on three clinical studies spanning over several development programs including simeprevir in different treatment combinations, durations and populations were held.

”We have a long and fruitful relationship with our global partner Janssen on simeprevir. These data show the commitment Janssen has for the HCV area, with studies of simeprevir in a wide range of patient populations and treatment regimens”, says Niklas Prager CEO of Medivir

Major findings in the studies presented:

Interferon free combinations

· In a phase II study up to 95% cure rates were achieved in HCV genotype (GT)1 infected patients treated with a 3-DAA combination of simeprevir, TMC647055/ritonavir and JNJ-56914845.

Interferon based triple combinations

· In the phase III TIGER study in treatment‐naive patients with chronic HCV GT1 infection conducted in China and Korea 89-91% were cured with simeprevir in combination with pegylated interferon (P) and ribavirin (R) for 12 weeks followed by PR for a further 12 or 36 weeks.

· The potential to shorten the total simeprevir plus PR treatment to 12 weeks in treatment-naïve hepatitis C patients is being investigated in an on-going phase III study. In the GT1 study arm 76% of the patients were eligible to shorten treatment and of those 66% achieved SVR12 (were cured). In the GT4 study arm 48% of the patients were eligible for shortened treatment and of those with evaluable outcome at the time of analysis 94% had achieved SVR4.

About the studies

HPC2001 – an interferon free study with 2 or 3 Direct Acting Antivirals (DAA) including simeprevir

This is an open phase IIa efficacy, safety and pharmacokinetic study of 12 weeks of simeprevir (SMV) in various interferon free combinations in HCV GT1 infected treatment naïve and prior relapser patients without cirrhosis. TMC647055 is a potent non-nucleoside polymerase inhibitor and JNJ-56914845 is a potent NS5A replication complex inhibitor.

Panel 1-3 included a 2-DAA combination (SMV + TMC647055/ritonavir) at different doses +/- ribavirin (n=7-12 per arm). Up to 86% of the patients achieved SVR12 (were cured) with ribavirin while up to 50% of the patients without addition of ribavirin achieved SVR12.

Panel 4 included a 3-DAA combination of SMV + TMC647055/ritonavir and 30 or 60 mg of JNJ-56914845 (n=22 per arm). This combination treatment resulted in overall SVR12 rates of 82% and 95% in the low and high dose groups of JNJ-56914845, respectively. All GT1b patients (100%) were cured regardless of JNJ-56914845 dose, while 71% and 93% of GT1a patients achieved SVR12 with the low and high dose of JNJ-56914845, respectively.

The combination treatments in all panels were generally well tolerated.

HPC3005 - the TIGER study in China and Korea

This is a phase III, randomised three-armed study evaluating simeprevir 150 mg (n=152) or 100 mg (n=153) or placebo (n= 152) plus PR for 12 weeks in treatment-naïve genotype 1 HCV patients in China and Korea. Patients in the simeprevir arms received PR alone for a further 12 or 36 weeks based on response-guided criteria (RGT). All patients in the placebo arm received a further 36 weeks of PR alone. Primary efficacy endpoint was sustained virologic response 12 weeks after planned end of treatment (SVR12).

The treatment was generally well tolerated and highly effective, with 89 % and 91 % SVR12 achieved in the 100 mg and 150 mg dose groups respectively, compared to 76% in the placebo arm; each simeprevir arm demonstrating superiority. 94% of the simeprevir-treated patients were eligible for the shorter 12 weeks follow-up treatment with PR and of those 94% achieved SVR12.

HPC3014 – shortening overall treatment to 12 weeks of simeprevir plus PR in HCV GT1 and GT4 patients

This is an on-going phase III, open-label study of efficacy and safety of 12 weeks treatment with SMV + PR in treatment-naıve GT1 and GT4 HCV infected patients with mild-to-moderate fibrosis (METAVIR F0-F2). The aim of the study is to assess whether overall treatment duration with simeprevir + PR can be shortened to 12 weeks, based on early viral kinetics including a Week 2 assessment. Patients not meeting predefined response criteria continued with additional 12 weeks of PR treatment.

Of the GT1 patients 76% (123 out of 163) were eligible for 12 weeks total treatment duration and of those 66% achieved SVR12. Higher SVR12 rates were seen in: IL28B CC genotype patients, patients with low baseline viral load, or those with mild fibrosis.

Of the GT4 patients 48% (24 out of 50) were eligible for 12 weeks total treatment and of those with evaluable outcome at time of analyses 94% (16 out of 17) had achieved SVR4.

Treatment with simeprevir and PR was generally well tolerated.

The following abstracts were presented:

“Efficacy safety and pharmacokinetics of 12 weeks of simeprevir in combination with TMC647055 ritonavir and JNJ-56914845 in genotype 1 hepatitis C virus infected patients” (presented by S Bourgeois).

“Efficacy safety and pharmacokinetics of 12 weeks of simeprevir in combination with TMC647055 and ritonavir with or without ribavirin in genotype 1 hepatitis C virus infected patients” (presented by S Bourgeois).

“Simeprevir plus peginterferon ribavirin in treatment naïve patients with chronic hepatitis C virus genotype 1 infection results from the phase III tiger study conducted in east asian patients living in China and Korea” (presented by L Wei).

“Simeprevir exposure in Asian treatment naive patients with chronic hepatitis C virus genotype 1 infection results from a population pharmacokinetic model in the phase III tiger study” (presented by E. Hoeben).

“Shortening overall treatment to 12 weeks of simeprevir plus pegylated interferon and ribavirin according to early virologic response in treatment naïve patients with chronic HCV genotype 4 infection and mild to moderate fibrosis” (presented by T Asselah).

“Shortening overall treatment to 12 weeks of simeprevir (smv) plus Peg-IFN and RBV in treatment naïve chronic hepatitis C (CHC) genotype 1 patients assessment of baseline and early (week 2) on treatment predictors of high SVR” (presented by T Asselah).

Further details can be found at www.apasl2015.org, at www.clinicaltrials.gov, and in Hepatol Int (2015) 9 (Suppl 1):S1–S391.

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 8.30 CET on 16 March 2015.

About Simeprevir (OLYSIO®)

Simeprevir is an NS3/4A protease inhibitor jointly developed by Janssen Sciences Ireland UC and Medivir AB and indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. Simeprevir efficacy has been established in HCV genotype 1 and HCV genotype 4 infected patients with compensated liver disease, including cirrhosis. Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB retains marketing rights for simeprevir in these countries under the marketing authorization held by Janssen-Cilag International NV. Simeprevir was approved for the treatment of chronic hepatitis C infection as part of an antiviral treatment regimen in combination with pegylated interferon and ribavirin in genotype 1 infected adults with compensated liver disease, including cirrhosis. Simeprevir was approved in September 2013 in Japan, in November 2013 in Canada and the U.S., in March 2014 in Russia and in July 2014 in Mexico and Australia.

In May 2014 simeprevir was granted marketing authorization by the European Commission (EC) for the treatment of adult patients with genotype 1 or genotype 4 chronic HCV. Following the EMA approval, it has so far been made available in several EU countries in conjunction with reimbursement. Simeprevir (OLYSIO) is marketed under the trade name Sovriad® in Japan and Russia, Galexos™ in Canada and Olysio® in the U.S. and European Union.

About Medivir

Medivir is a research based pharmaceutical company with a research focus on infectious diseases and oncology. We have a leading competence within protease inhibitor design and nucleotide/nucleoside science and we are dedicated to develop innovative pharmaceuticals that meet great unmet medical need. Our commercial organization provides a growing portfolio of specialty care pharmaceuticals on the Nordic market. Medivir is listed on the Nasdaq Stockholm Mid Cap List.

This information was brought to you by Cision http://news.cision.com

Contacts

EVP Development
Charlotte Edenius MD, PhD
mobile: +46 (0)73 386 42 46
or
Medivir AB
Ola Burmark, CFO
mobil: +46 (0)725-480 580

Sunday, October 26, 2014

3 die after being administered SOVRIAD™ (simeprevir sodium) Hepatitis C drug

3 die after being administered hepatitis C drug

The health ministry said Friday three people have died after taking the hepatitis C drug Sovriad, and it has ordered the distributor to revise the drug packaging to say usage should stop when indicated by a patient blood test.

The ministry also ordered the maker and distributor, Janssen Pharmaceutical K.K., to notify doctors and hospitals in writing of the change.

The package insert already warns of possible deterioration of liver function from use of the drug, known generically as Simeprevir Sodium. The ministry directed the packaging also say usage should be discontinued if a blood test indicates certain abnormalities.

According to the Ministry of Health, Labor and Welfare, taking the drug will increase "bilirubin" by decomposing hemoglobin in the blood and may aggravate dysfunction of the liver and kidney.

Three patients in their 40s to 60s who were taking the drug died in connection with such symptoms, it said.

Since the drug was put on sale last December, about 19,000 people in Japan had used it by the end of September.

Friday, November 22, 2013

Simeprevir and Sofosbuvir-The Next Wave of Hepatitis C Treatment

 Medscape Gastroenterology

The Next Wave of Agents for Treatment of Hepatitis C

William F. Balistreri, MD
November 21, 2013

For several years, the recommended standard of care for patients with chronic hepatitis C virus (HCV) infection consisted of a combination of pegylated interferon (PEG-IFN) and ribavirin (RBV). On the basis of understanding of the biology of the virus and identification of proteins involved in HCV replication came the development of agents that inhibited the HCV protease and polymerase enzymes.

A few years ago, the US Food and Drug Administration (FDA) approved 2 direct-acting antiviral agents for the treatment of HCV genotype 1: the NS3 protease inhibitors telaprevir and boceprevir. The American Association for the Study of Liver Diseases guidelines[1] were updated to recommend triple therapy consisting of one of these protease inhibitors given in combination with PEG-IFN and RBV. This recommendation was based on results of clinical trials of this combination, which showed significantly improved sustained virologic response (SVR) rates. Although this triple therapy is generally well tolerated, troublesome side effects occur in many patients. The good news is that the guidelines may once again be revised thanks to the emergence of the next wave of direct-acting antivirals.

Simeprevir and Sofosbuvir

Simeprevir is a potent, once-daily oral investigational NS3/4A protease inhibitor that was shown to be effective when coadministered with standard therapy (PEG-IFN and RBV) for treatment of HCV genotype 1 infection both in treatment-naive patients and in patients who did not respond to standard therapy.[2-10]

Primary efficacy and safety data from clinical trials of simeprevir in patients with genotype 1 chronic HCV infection were in part responsible for the recommended FDA approval of this agent on October 24, 2013. The FDA's Antiviral Drugs Advisory Committee recommendation was unanimous, commenting that the available data overwhelmingly supported approval of the simeprevir, PEG-IFN, and RBV combination for HCV genotype 1 infection in treatment-naive patients and in those who had relapse after previous therapy. The committee reviewed safety and efficacy data from a series of double-blind, placebo-controlled trials -- phase 3 studies of treatment-naive patients and patients with previous relapse, and a phase 2b study involving patients with previous relapse and nonresponders.

For example, simeprevir (TMC435) administered once daily in combination with PEG-IFN and RBV was associated with SVR 12 weeks after the end of treatment (SVR12) in approximately 80% of treatment-experienced (relapsed) genotype 1 chronic hepatitis C patients. The SVR12 rate was less than 40% in patients receiving placebo plus PEG-IFN and RBV. Treatment failure rates and relapse rates were lower in simeprevir recipients than placebo recipients.

Simeprevir was shown to be generally safe and well tolerated, even among patients with advanced liver fibrosis. The most common adverse events were fatigue, headache, and influenza-like illness.

The FDA Advisory Committee did, however, further recommend that patients be screened for the commonly occurring Q80K mutation because simeprevir was found to be less effective in the presence of this mutation. They also recommended that the label should indicate that sunburn is a common side effect. More information about the simeprevir clinical trials can be found at ClinicalTrials.gov.

Soon to follow was the recommended FDA approval of sofosbuvir, a nucleotide analog that inhibits NS5B-directed HCV replication; this agent has also been shown to be highly effective. Sofosbuvir in combination with standard therapy was associated with SVR12 rates of 90% compared with 58% in placebo-treated patients.[11,12]                        

Both agents will be indicated for treatment of patients with HCV genotype 1, but only in combination with PEG-IFN and RBV. These drugs represent an advance in management -- they promise to be capable of inducing high SVR rates with 1 pill per day, shorter duration of therapy, better tolerability, and no resistance development. The 1-pill-daily regimen simplifies the treatment strategy; however, the cost and side effects are likely to remain high.

A Glimpse of the Future in HCV Treatment

There is an even higher degree of optimism, however, because recent studies may usher in the next wave of treatment strategies for HCV infection. In my opinion, the goal for treatment in terms of efficacy, safety, and tolerability is an IFN-free regimen. Simeprevir is being studied in phase 2 IFN-free trials with and without RBV and in combination with a host of other agents that act synergistically to inhibit HCV replication, and which include all oral regimens. For example, studies in progress suggest that high SVRs can be achieved in patients treated with simeprevir and sofosbuvir together, with and without RBV.

I will end by offering a glimpse of the future. Currently under evaluation in clinical studies are second-generation protease inhibitors and small-molecule drugs that inhibit other viral enzymes. Drug cocktails that target multiple HCV enzymes simultaneously may ultimately become the standard of treatment, as in the current strategy for the management of infection with HIV.

The bottom line is that these exciting advances in antiviral therapy will lead to significant improvements in response rates with reduced adverse effects. These advantages may lower the threshold for HCV treatment for both patients and physicians.

It is important to note, though, that at present only a minority of HCV-infected patients may benefit because of multiple barriers that have been identified and that impede delivery of therapy. A major issue is inadequate case-finding, an obstacle that could be overcome by widespread screening. The Centers for Disease Control and Prevention recently advised enhanced testing; their guidelines state that many persons who test positive for hepatitis C do not receive the necessary follow-up to determine whether they require medical care. Therefore, enhanced efforts to improve awareness, education, and specialist availability are needed.

The high prevalence of HCV infection worldwide should also stimulate expanded efforts in primary prevention, including vaccine development. Perhaps we can soon wave good-bye to HCV!

http://www.medscape.com/viewarticle/814701_3

Wednesday, November 20, 2013

Simeprevir Approved for Hepatitis C in Canada

Simeprevir Approved for Hep C in Canada

Medivir AB announced that Health Canada has approved simeprevir for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin in adults with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin.
 
Simeprevir received priority review status and is the first treatment for CHC to be approved for once-daily administration with pegylated interferon and ribavirin in Canada.
 
In Canada, for a drug to receive priority or accelerated review, it must show effective treatment of a serious, life-threatening or severely debilitating disease or condition for which no drug is presently marketed in Canada. Or, it must show a significant increase in efficacy and/or decrease in risk so that the overall benefit/risk profile is improved over existing therapies for a disease that is not adequately managed by a drug already marketed in Canada.
 
“Canada is the second market where simeprevir has been approved and will be a new agent in the treatment of hepatitis C. The priority review process shows the importance of offering new treatment options also for the hardest to treat patients and we are very happy that both patients and physicians are given new hope,” said Maris Hartmanis, CEO, Medivir.
 
The approval of simeprevir in Canada is based on four pivotal studies of patients with CHC genotype 1 infection: in treatment-naïve patients (QUEST-1 and QUEST-2), and in patients who have failed prior treatment with pegylated interferon and ribavirin; in PROMISE (prior relapsers) and ASPIRE (prior non-responders).
 
Results from a pooled analysis of QUEST-1 and QUEST-2 demonstrated that 80% of treatment-naïve patients in the group receiving simeprevir achieved sustained virologic response 12 weeks after the end of treatment (SVR12), compared with 50% of patients in the placebo groups. In PROMISE, 80% of prior-relapser patients in the simeprevir arm of the study achieved SVR12 compared with 37% of patients in the placebo group. Results from ASPIRE demonstrated that use of simeprevir led to sustained virologic response 24 weeks after the end of treatment (SVR24) in 62% of prior partial responder patients and 58% of prior-null responder patients compared with 6% and 15% of prior partial and null-responder patients in the placebo groups, respectively.
 
Date: November 20, 2013
Source: Medivir

Related - Hot Topics

Simeprevir Approved in Japan and Canada

Simeprevir was approved in Japan  September 2013 and in Canada November 20th for the treatment of HCV genotype 1, in combination with peginterferon alfa and ribavirin in adults with compensated liver disease, including cirrhosis, who are treatment-naïve or who have failed previous interferon therapy (pegylated or non‑pegylated) with ribavirin.

FDA Updates - Sofosbuvir and Simeprevir

Both Drugs Receive Positive FDA reviews by the advisory board

In October the Antiviral Drugs Advisory Committee  recommend the approval of Gilead's Sofosbuvir, a nucleotide analog NS5B polymerase inhibitor in combination with just ribavirin for treating adult HCV genotypes 2/3 and in combination with pegylated interferon/ribavirin for genotype 1 and 4 treatment-naive patients and Johnson & Johnson's Simeprevir a protease inhibitor in combination with pegylated interferon and ribavirin for the treatment of adult genotype 1 patients with compensated liver disease, including cirrhosis.

For detailed information please download the FDA review package for sofosbuvir and simeprevir.

The FDA does not have to follow the advice of its panels, but most often does. The U.S. health regulators are scheduled to decide whether to approve sofosbuvir by Dec. 8, and simeprevir by Nov. 27.

Friday, November 15, 2013

CME Video: Emerging Treatment Options for Hepatitis C Genotype 3,2 and 1 Patients

Hello folks,
Clinical Care Options (CCO) launched a series of video modules with three different case scenarios exploring HCV treatment choices, durations, and outcomes in genotype 3, 2, and 1 patients.

For instance in the first module the panel weighs in on the clinical trial data of investigational agents sofosbuvir and simeprevir in treatment naïve and experienced genotype 3 patients. The text only for "Case 1 " is provided below, an expert video discussion for each case is available in the module. 

Other topics include; treatment options for a new class of null responders who failed telaprevir or boceprevir and treating recurrent HCV after liver transplantation. 

A free quick registration is required 

Advanced HCV Treatment Topics
Fred Poordad, MD, moderates a case-based panel discussion exploring complex management issues in HCV-infected patients with Nezam H. Afdhal, MD, FRCPI, Douglas T. Dietrich, MD, Paul Y. Kwo, MD, and Norah Terrault, MD, MPH.

Released: 11/7/2013

Case 1: A Treatment-Experienced Patient With Genotype 3 HCV

Fred Poordad, MD:The patient is a 57-year-old white male with genotype 3a HCV infection and previous treatment failure on peginterferon 2a and ribavirin. He is now asking about his options for retreatment. He has no specific records of his past treatment, and his previous HCV RNA levels are unknown. He indicates he developed anemia while on therapy, with ribavirin being held for an unknown period. His current HCV RNA is 1.2 million IU/mL; liver enzyme studies determine his alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are elevated at 125 U/L and 114 U/L, respectively, but the rest of his laboratory examinations are within normal limits. His ultrasound shows his liver and spleen to be of normal size and a FibroTest identifies F0-F2 fibrosis. 

The first consideration is whether you would perform any additional tests to evaluate the patient’s liver histology?

Douglas T. Dieterich, MD:I would certainly want more information because my own experience with FibroTest has been less than ideal. At my center, we typically use transient elastography because we have it available. I wouldn’t order a liver biopsy.

Paul Y. Kwo, MD:My view is that the results of a liver biopsy would be helpful. The serum markers present 1 part of the picture; however, in this instance, the management approach will depend on the liver histology, making the biopsy results very helpful.


Norah Terrault, MD, MPH:I agree that the patient’s fibrosis stage is critical information, and the F0-F2 score on the FibroTest leaves considerable room for uncertainty. The patient’s platelet count is also concerning. A biopsy may be useful to help determine whether to delay treatment. 

It is important to remember that every test has an error rate, and all the available data have to come together and make sense when you evaluate a given patient. If 1 of the tests does not seem consistent with other aspects of the patient presentation, it is important to seek more information until you are confident in making the right decision.

Fred Poordad, MD:In this case, we did biopsy the patient, and the results indicated Stage 3 fibrosis by Metavir score.

Disease Outcomes and Treatment Outcomes in Genotype 3 HCV

Fred Poordad, MD:Until recently, genotype 2 and genotype 3 HCV have been classified as a single entity. However, in recent years, differences between these genotypes have become more clearly recognized. Disease progression rates are faster in genotype 3 compared with genotype 2.[1] As long ago as 2007, Shiffman and colleagues[2] demonstrated that patients with genotype 2 HCV treated with peginterferon/ribavirin experience an approximately 10% higher rate of sustained virologic response (SVR) compared with those infected with genotype 3 HCV with the same regimen. Importantly, rapid virologic response (RVR) rates are lower in genotype 3 and, especially in patients with genotype 3 without RVR, 16 weeks of therapy is inadequate to achieve SVR.[2] Further, patients experience higher relapse rates with genotype 3.[3]

Nezam H. Afdhal, MD, FRCPI:Disease progression rates are really a difficult question and determining disease progression rates is complex. There are no good cohort studies that have followed untreated patients for 20 or 30 years to show this kind of retrospective data. However, numerically speaking, patients with genotype 3 HCV infection tend to have more liver disease at the time of presentation—whether that means the true rate of progression is different or not is unclear. Additionally, genotype 3 HCV infection is associated with more hepatic steatosis; does that affect progression? Genotype 3 HCV infection in the United States and Europe is a disease of young intravenous (IV) drug users, while in the rest of the world it is very predominant in India and Pakistan, where there is significant morbidity and mortality associated with cirrhosis, liver cancer, and liver failure from this disease. Overall, we do see a lot more disease in patients with genotype 3 HCV infection, but I am not sure if this is due to a difference in the rate of progression in this patient population.

Norah Terrault, MD, MPH:I agree that it is difficult to judge disease progression, but there are some emerging data that the genotype might be a predictor of outcomes. Whether this outcome is driven by genotype 3 HCV itself or by accompanying cofactors is unclear.

Fred Poordad, MD:Van der Meer and colleagues[4] demonstrated an approximately 2-fold increased risk of mortality in patients with genotype 3 HCV infection compared with patients without genotype 3 infection. Importantly, curing genotype 3 HCV results in a significantly lower mortality rate compared with patients who are treated but do not achieve an SVR. Furthermore, older patients with genotype 3 HCV, higher levels of fibrosis, diabetes, or a history of alcohol use are less likely to do well.[4]

Douglas T. Dieterich, MD:That has been my experience as well. Alcohol, diabetes, and genotype 3 HCV infection are all associated with steatosis in the liver which may increase the fibrosis rate, leading to higher mortality. As a consequence, patients with genotype 3 HCV who fail treatment with peginterferon/ribavirin are some of the most difficult to treat outside of a clinical trial.

Emerging Treatment Options for Genotype 3 HCV

Fred Poordad, MD:The interferon-free combination of the nucleoside analogue sofosbuvir with ribavirin has shown promise in the treatment of genotypes 2 and 3 HCV, and at the time of writing has been submitted for approval for these genotypes.

The phase III Fission trial was a randomized, open-label, active-control, noninferiority study comparing 12 weeks of sofosbuvir plus ribavirin with 24 weeks of peginterferon/ribavirin in treatment-naive patients with genotype 2 or 3 HCV infection. The overall SVR rates were 67% for both sofosbuvir plus ribavirin and peginterferon/ribavirin.[5] Subanalysis based on HCV genotype found that patients with genotype 2 infection had a 97% SVR rate with sofosbuvir plus ribavirin compared with 78% SVR rate with peginterferon/ribavirin. However, the sofosbuvir plus ribavirin regimen for patients infected with genotype 3 HCV achieved an SVR of 56% vs a 63% SVR rate with peginterferon/ribavirin. These results indicate the noninferiority endpoint was met, but for genotype 3 HCV infection, the data are clearly not as satisfying as hoped.

The blinded, active-controlled phase III FUSION study explored treatment with 12 weeks of sofosbuvir plus ribavirin, followed by 4 weeks of matching placebo, or 16 weeks of sofosbuvir plus ribavirin in treatment-experienced patients with genotype 2 or 3 HCV infection. After 12 weeks of treatment in patients with genotype 3 HCV infection, the SVR rate was only 30%.[6] However, the additional 4 weeks of treatment doubled the SVR rate to 62%.

Now, go to the next page to see a video of the faculty discussion of these data.

Continue to CCO........



Wednesday, November 13, 2013

Costs for Hepatitis C Treatment Skyrocket

Medscape

Costs for Hepatitis C Treatment Skyrocket
Miriam E. Tucker
November 13, 2013

WASHINGTON, DC — The expense of telaprevir-based triple therapy for hepatitis C — including adverse event management — is $189,000 per sustained viral response, report investigators.

"Our findings indicate that the benefit-cost ratio is lower than projected, based on results of the registration trials," lead investigator Andrea Branch, MD, from the Icahn School of Medicine at Mount Sinai in New York City.

Kian Bichoupan, MBS, who is Dr. Branch's first-year PhD clinical research student, presented the results here at The Liver Meeting 2013.

The number seemed to alarm session comoderator Sammy Saab, MD, from the David Geffen School of Medicine at UCLA, who called it "very surprising." It is "at least double what we think the cost is. I didn't know the cost of actually curing someone was so high," he said.

It is expected that 2 new direct-acting antiviral agents for the treatment of hepatitis C, simeprevir and sofosbuvir, will be approved by the US Food and Drug Administration (FDA) on December 8. Both have far better adverse-event profiles than telaprevir-based regimens, but the degree to which the cost-effectiveness calculation will change depends on their price, which hasn't yet been announced, Dr. Saab explained.

The benefit-cost ratio is lower than projected.

Before telaprevir received FDA approval in May 2011, the standard of care for genotype 1 hepatitis C was 48 weeks of pegylated interferon and ribavirin. With that regimen, the sustained viral response ranged from 40% to 50%. With the addition of telaprevir to the peginterferon and ribavirin regimen, response rates increased to 64% to 75%, but adverse events and costs also rose.

Previous studies have shown that peginterferon and ribavirin dual therapy costs $70,364 per sustained viral response in patients with genotype 1 hepatitis C. Data from phase 3 registration trials suggest that telaprevir-based triple therapy is cost-effective, but real-world data have been unavailable until now, Bichoupan said.

The researchers evaluated 147 patients who initiated telaprevir-based triple therapy at Mount Sinai. The mean age of the cohort was 56 years, and 68% of the cohort was male, 19% was black, 46% did not respond to previous hepatitis C treatment, and 35% had advanced fibrosis or cirrhosis.

They calculated the cost of the therapy itself and the management of adverse events from Medicare, the Agency for Healthcare Research and Quality, and other sources.

Sustained viral response was achieved by 44% of patients. At 48 weeks, the cost of telaprevir was $55,273, of peginterferon was $30,418, and of ribavirin for $4926. Telaprevir accounted for 61% of the $90,617 total, Bichoupan noted.

Adverse events, primarily anemia, accounted for 8% of the total cost; 48% of the patients required treatment with epoetin alpha, 9% needed blood transfusions, 8% were treated with granulocyte colony-stimulating factor (G-CSF), 13% required hospitalization, and 10% made emergency department visits.

Total costs were $664,083 for epoetin alfa, $29,007 for G-CSF, and $12,644 for transfusions.

The total cost of treating hepatitis C was higher for the 65 patients who achieved sustained viral response than for the 82 who did not ($6.33 vs $5.24 million).

The median cost per patient was $83,509. The researchers multiplied that by the reciprocal of the 44% sustained viral response (2.27), and arrived at $188,859 per response.

The cost per sustained viral response was lower for treatment-naïve than for previously treated patients ($158,403 vs $199,134). For patients with advanced liver fibrosis, the cost was $185,484. For those with less severe fibrosis, the cost jumped to $256,977, Bichoupan reported.

He pointed out that this study started when telaprevir had just reached the market, and that outcomes might improve over time with better strategies for preventing adverse events.

Dr. Branch told Medscape Medical News that these data can't determine whether nearly $200,000 per sustained viral response is cost-effective, because not enough is known about the cost savings associated with such a response.

Better Options

Other investigators have compared health costs for patients who achieve a sustained viral response with costs for patients with chronic hepatitis C infection. However, "this is not the best way to do the analysis because patients who achieve a sustained viral response may be healthier than patients who do not," Dr. Branch noted.

Dr. Saab said he agrees that the cost figures are likely to improve as experience with the drugs increases. However, he noted that telaprevir will likely disappear soon after the expected FDA approval of simeprevir and sofosbuvir.

Dr. Branch echoed this opinion. Telaprevir-based regimens "are only appropriate for patients who cannot wait even a few months for newer regimens to complete the FDA review and approval process," she said.

This study was supported in part by Gilead Sciences, the National Institute of Drug Abuse, and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Saab is a consultant to Bristol-Myers Squibb.

The Liver Meeting 2013: American Association for the Study of Liver Diseases (AASLD). Abstract 244. Presented on November 5, 2013

Of Interest @ HCV New Drugs
How Much? A Battle Over The Cost Of The New Hepatitis C Drugs
According to an article over at Pharmalot, Wall Street has estimated sofosbuvir to reach $80,000 to $90,000, per patient in the US. The high cost will put these drugs out of reach for low and middle-income countries. Columnist Ed Silverman mentioned a presentation at this months liver meeting which suggests a much lower cost then predicted by investment analysts. Andrew Hill of Liverpool University and colleagues presented a new analysis of predicted minimum costs to produce four next generation HCV DAAs, currently in Phase 3 development. The poster was also presented earlier this year at the 7th IAS Conference. Here is the cost prediction in Hill's paper: $20-63 for a 12-week treatment of ribavirin, $10-30 for daclatasvir, $68-136 for sofosbuvir, $100-210 for faldaprevir and $130-270 for simeprevir  (view the full analysis here)


Tuesday, November 12, 2013

Simeprevir SVR in Treatment-Naïve and Treatment-Experienced Geno 1 Chronic Hepatitis C Patients

Simeprevir Administered Once Daily Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Patients

Beerse, Belgium (Nov. 11, 2013) Janssen R&D Ireland (Janssen) today announced the presentation of new data for the new generation protease inhibitor simeprevir (TMC435) in the treatment of genotype 1 chronic hepatitis C (HCV) in treatment-naïve and treatment-experienced adult patients with compensated liver disease. In analyses of the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, the efficacy of simeprevir was observed in HCV patients considered difficult to treat, including patients with the IL28B TT genotype and METAVIR scores of F4.

HCV is a major problem in the EMEA region, where an estimated 15 million people are living with the disease.1 Many patients living with chronic HCV are in need of treatment and the genotype of the virus often determines how efficacious treatment will be.2

"Patients with certain baseline characteristics can be more likely to fail or relapse after prior treatment," said Ira Jacobson, M.D., simeprevir clinical trial investigator, chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, Weill Cornell Medical College, and attending physician, New York-Presbyterian Hospital/Weill Cornell Medical Center, United States. "The breadth of simeprevir data presented at The Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) reinforce the potential of simeprevir as an effective treatment option in multiple patient populations, including patients who are considered difficult to treat, and will offer important guidance to physicians once simeprevir is approved."

On October 24, the U.S. Antiviral Drugs Advisory Committee of the FDA voted unanimously (19-0) to recommend simeprevir 150mg capsules administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic HCV in adult patients with compensated liver disease. A Marketing Authorisation Application was submitted to the European Medicines Agency seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic HCV in April 2013. Simeprevir was approved in September 2013 in Japan, for the treatment of genotype 1 HCV. Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. UK/HCV/1113/0021

Pooled Analysis from QUEST-1 and QUEST-2 Confirms Clinical Benefit of Simeprevir in Sub-Populations of Patients (Abstract 1122)

In the Phase 3 QUEST-1 and QUEST-2 studies, 80% of treatment-naïve patients treated with simeprevir in combination with pegylated interferon and ribavirin achieved the primary endpoint of sustained virologic response 12 weeks after the end of treatment (SVR12) compared to 50% of patients treated with placebo plus pegylated interferon and ribavirin. The analysis, which included patients considered difficult to treat, found that 61% of patients with the IL28B TT genotype, 60% of patients with a METAVIR score of F4 and 75% of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 21%, 34% and 47% of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 58% of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 52% of patients treated with placebo in combination with pegylated interferon and ribavirin, but the difference was not statistically significant. 3% of patients treated with simeprevir discontinued treatment early due to an adverse event, compared to 2% of patients treated with placebo.

Analysis from PROMISE Reinforces Efficacy of Simeprevir in Sub-Populations of Patients (Abstract 1092)

In the pivotal Phase 3 PROMISE study, 79% of treatment-experienced HCV patients treated with simeprevir in combination with pegylated interferon and ribavirin who previously experienced a relapse after prior treatment with pegylated interferon-based therapy achieved the primary endpoint of SVR12 compared to 37% of patients treated with placebo plus pegylated interferon and ribavirin. In this sub-analysis, among patients considered difficult to treat, 65% of patients with the IL28B TT genotype, 74% of patients with a METAVIR score of F4 and 70% of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 19%, 26% and 28% of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 47% of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 30% of patients treated with placebo in combination with pegylated interferon and ribavirin. The most common adverse events in patients treated with simeprevir combined with pegylated interferon and ribavirin in the first 12 weeks were fatigue, headache and influenza-like illness.

"The data presented at AASLD offers further evidence of simeprevir’s efficacy in difficult to treat patient types," said Dr Maria Beumont, medical lead for simeprevir, Janssen. "Following the recent positive vote from the FDA’s Antiviral Drugs Advisory Committee to recommend approval of simeprevir, we look forward to making simeprevir available to patients living with chronic HCV in need of treatment in the near future, while we continue to evaluate the role of simeprevir as part of different HCV treatment combinations."

About Simeprevir

Simeprevir (TMC435) is a new generation NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, currently in Phase III development. Simeprevir works by blocking the viral protease enzyme that enables HCV to replicate in host cells. To date, more than 3,700 patients have been treated with simeprevir in clinical trials. UK/HCV/1113/0021 Page 3

Janssen Therapeutics EMEA, a division of Janssen Pharmaceutica NV has the commercialisation rights of simeprevir in Europe, Middle East & Africa. Medivir AB will commercialise the product in the Nordic countries.

In October, Janssen Pharmaceuticals, Inc. acquired the investigational compound GSK2336805, an NS5a replication complex inhibitor in Phase 2 development for the treatment of chronic HCV, from an affiliate of GlaxoSmithKline plc. Since being acquired, the compound has been renamed JNJ-56914845. Janssen Pharmaceuticals plans to initiate Phase 2 studies to evaluate the use of JNJ-56914845 in interferon-free combinations with simeprevir and TMC647055, the company’s non-nucleoside polymerase inhibitor, for the treatment of chronic HCV in adult patients with compensated liver disease.

For additional information about simeprevir clinical studies, please visit: https://www.clinicaltrialsregister.eu or www.clinicaltrials.gov.

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver that affects approximately 150 million people worldwide, and causes 350,000 deaths annually.2 In the European region alone the incidence rate is 8.7 per 100,000 and leads to 86,000 deaths annually.1

When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure. It is the leading cause of primary liver cancers in Europe.3

About Janssen R&D Ireland

At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world.

Janssen R&D Ireland is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

Janssen Therapeutics EMEA is fully dedicated to HCV and simeprevir. Janssen-Cilag International NV is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit www.janssen-emea.com and www.janssentherapeutics-emea.com for more information. UK/HCV/1113/0021 Page 4

References

1. World Health Organisation Regional Office for Europe. Hepatitis data and statistics. http://www.euro.who.int/en/health-topics/communicable-diseases/hepatitis/data-and-statistics . Last accessed October 2013.

2. World Health Organisation Media Centre: Hepatitis C Fact Sheet No. 164; July 2013.

http://www.who.int/mediacentre/factsheets/fs164/en/ . Last accessed October 2013.

3. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology 2011;55:245–264.

Monday, November 11, 2013

AASLD Sofosbuvir/Simeprevir-What Is The Minimum costs to produce Hepatitis C Direct Acting Antivirals

Dec 9 - Fair Pricing Coalition Condemns Gilead Sciences on the High Price of New Hepatitis C Drug Sovaldi™, and Urges Rapid and Wide Dissemination of Support Program Details for Uninsured and Underinsured People Living with Hepatitis C

Nov 26 - Now FDA Approved Olysio (simeprevir) - The New Kid On The Block
OLYSIO (Simeprevir) Cost? - Janssen has priced Olysio at a wholesale acquisition price of $22,120 per bottle of 28 capsules (150 mg capsules), which is an approximately one-month supply. That's roughly $66,360 for a three-month course.

Nov 13 -Medscape - Costs for Hepatitis C Treatment Skyrocket

AASLD-What Is The Minimum costs to produce Hepatitis C Direct Acting Antivirals

A third wave of anti HCV DAA agents are currently moving through the pipeline, two new DAAs have already been reviewed by the Antiviral Drugs Advisory Committee, Gilead's Sofosbuvir and Johnson & Johnson's Simeprevir.

The result of the whole process is expected to be decided by the FDA in early December for Sofosbuvir and late November for Simeprevir.

Additionally, other new DAAs in Phase III clinical trials are able to increase SVR and shorten therapy in a significant proportion of both treatment-naïve and treatment-experienced chronic HCV infected patients.

However the drugs are expected to be expensive, patients in the US could pay anywhere from $60,000 - $100,000 per treatment. The cost for these life saving drugs will be out of reach for patients in developing countries and the uninsured.

Analysis Of Predicted Minimum Costs To Produce Hepatitis C Direct Acting Antivirals

At this months AASLD, Andrew Hill of Liverpool University and colleagues presented a new analysis of predicted minimum costs to produce Direct Acting Antivirals for the treatment of hepatitis C. The minimum cost of 12 weeks of treatment with each DAA(see below) was calculated assuming a production cost per gram of HCV DAA between 1-10 times the equivalent HIV antiretroviral and based on compound properties including chemical structure, complexity of synthesis, and daily dose. The analysis was also presented earlier this year at the 7th IAS Conference

Predicted Minimum Costs

The analysis predicted  $20-63 for a 12-week treatment of ribavirin,  $10-30 for daclatasvir, $68-136 for sofosbuvir, $100-210 for faldaprevir and $130-270 for simeprevir see charts below.

The complete analysis is available for downloading here or view the predicted costs/slides provided below.

AASLD, Washington DC

Minimum costs to produce Hepatitis C Direct Acting Antivirals

Andrew Hill and Saye Khoo, Department of Pharmacology and Therapeutics, Liverpool University, UK Bryony Simmons, Imperial College, London, UK Nathan Ford, University of Cape Town, South Africa

64th Annual Meeting of AASLD, Washington DC, United States of America, November 2013 [Poster 1097]

TREATMENT COVERAGE IS LOW EVEN IN DEVELOPED COUNTRIES

Despite the long term morbidity & mortality associated with untreated hepatitis C, data suggests that relatively few patient are being treated.

In Europe only 3.5% of infected individuals received antiviral treatment by the end of 2010 (ranging from 16% in France to <1% in Poland)

In the USA only 21% of infected individuals had received treatment by the end of 2007

Reasons for under - treatment:
• Under - diagnosis (80% of HCV cases are asymptomatic)
• Limitations of currently available medication
• The very high prices of drug treatment

THE STIMATED COST OF CURRENT TREATMENT (UK & US ESTIMATES )




HEPATITIS C GLOBAL PREVALENCE BY COUNTRY (2010)


HEPATITIS C GLOBAL PREVALENCE BY COUNTRY(2010)





PATENT EXPIRY DATES




DAA COMBINATIONS : INTERFERON - FREE REGIMENS 
Several combinations of two DAAs (with or without RBV) can cure HCV (SVR) in the majority of treatment - naïve, genotype 1 patients, without the use of interferon:



Continued......



RATIONALE

DAAs for HCV infection have similar mechanisms of action and chemical structures to antiretrovirals for HIV infection.

Generic antiretrovirals are currently manufactured at very low cost, for treatment of over ten million people with HIV in low and middle income countries.

Minimum costs of HIV antiretrovirals are 0.2-0.9/g of drug for nucleoside analogues, 0.5/g for nucleotide analogues, and 0.7-2.1/g for protease inhibitors.

For widespread treatment of HCV in developing countries to be feasible, we need short-course of antiviral treatment available at very low cost.

Using the cost of HIV drugs as a framework, we can make estimates for the potential cost of HCV DAAs

























AASLD Coverage

Commentary/Abstracts/Videos @ Healio

Capsule Summaries, review by experts and slides @ Clinical Care Options CCO

Commentary/Abstracts with coverage by Liz Highleyman @ hivandhepatitis.com

Slides/Abstracts @ NATAP

CME/CE with commentary by Michael Smith @ MedPage Today

Tuesday, November 5, 2013

AASLD - COSMOS study with Simeprevir and Sofosbuvir in cirrhotic and non-cirrhotic HCV genotype 1 patients


Results from the COSMOS study with Simeprevir and Sofosbuvir in cirrhotic and non-cirrhotic HCV genotype 1 patients presented at AASLD

Stockholm, Sweden — Medivir AB (OMX: MVIR) today announced data from the interferon-free COSMOS study demonstrating safety and efficacy of the investigational protease inhibitor simeprevir (TMC435) in combination with the investigational nucleotide inhibitor sofosbuvir (GS-7977), with and without ribavirin, in genotype 1 chronic hepatitis C adult patients with compensated liver disease was presented at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, D.C. during the late-breaking oral session on Monday, November 4.

“The high sustained virologic response (SVR) rates seen in genotype 1 patients with prior null response and in treatment-naïve and prior null response patients with advanced liver disease, in the COSMOS study, are highly encouraging. These difficult-to-cure patient groups are in urgent need of efficacious treatment options which today are lacking” says Charlotte Edenius, EVP Development, Medivir.

COSMOS - Study Design
COSMOS is a phase IIa, randomized, open-label study investigating the safety and efficacy of simeprevir in combination with sofosbuvir, with and without ribavirin, for either 12 or 24 weeks. The study enrolled HCV genotype 1 patients who were prior null responders to treatment with interferon and ribavirin with METAVIR F0-F2 scores (cohort 1, n=80), or treatment-naïve patients and prior null responders with METAVIR F3-F4 scores (cohort 2, n=87).

Final sustained virologic response 12 weeks after the end of treatment (SVR12) data from cohort 1 in previous null responder patients with METAVIR scores F0-F2 were presented, along with sustained virologic response 4 weeks after the end of treatment (SVR4) data from the 12 week arms of cohort 2 in treatment-naïve and previous null-responder patients with METAVIR scores F3-F4. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver. Liver fibrosis is scored on a four-point scale.

In cohort 1, 77 percent of the patients had genotype 1a (GT1a) subtype with 50 percent of those having baseline Q80K polymorphism. Seventy percent had IL28B CT genotype, 24 percent had IL28B TT genotype and 59 percent had METAVIR score F2.

In cohort 2, 78 percent of patients had GT1a subtype with 40 percent of those having baseline Q80K polymorphism. Fifty-six percent had IL28B CT genotype, 23 percent had IL28B TT genotype, 47 percent had METAVIR score F4 (cirrhosis) and 54 percent were prior null responders.

COSMOS – Efficacy Summary
In cohort 1, the SVR12 rate was 93 percent in genotype 1 null-responder patients with METAVIR scores of F0-F2 treated with simeprevir and sofosbuvir for either 12 or 24 weeks.

In an interim analysis of cohort 2, the SVR4 rate was 100 percent in both genotype 1 treatment-naive patients and prior null-responder patients with METAVIR scores of F3-F4 treated with simeprevir and sofosbuvir for 12 weeks.

In a pooled analysis of the 12-week treatment arms in cohorts 1 and 2, SVR4 was achieved among patients treated with simeprevir and sofosbuvir with or without ribavirin, in 96 percent of patients with IL28B non-CC genotype, 91 and 100 percent of patients with a METAVIR score of F4, respectively, and 95 percent of prior null responders.

All patients who completed treatment were HCV RNA undetectable at end of treatment and there were no viral breakthroughs in either cohort 1 or 2. The COSMOS study interim results show no benefit from adding ribavirin to simeprevir and sofosbuvir in this difficult to treat groups of hepatitis C patients and that 12 week treatment may confer similar clinical benefit to 24 week treatment.

Efficacy results with 150 mg simeprevir (SMV) and 400 mg sofosbuvir (SOF) once daily with or without ribavirin (RBV). Intent-to-treat (ITT) population.

 
**SVR4 data was only available for 12-week arms at time of interim analysis cut-off

COSMOS - Summary Safety
The most common adverse events in both treatment arms were fatigue, headache, nausea and insomnia. Rash, itching, anemia and bilirubin increases occurred mainly in the ribavirin-containing arms of treatment. Four percent of patients (2/54) treated with simeprevir and sofosbuvir with ribavirin and 7 percent of patients (2/31) treated with simeprevir and sofosbuvir without ribavirin, respectively, discontinued treatment due to an adverse event in the 24 week arms, while no patients (0/82) in the 12 week arms discontinued treatment due to an adverse event at the time of this analysis.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR
Mobile: +46 708 537 292.

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 4.30 p.m. EST on 4 November 2013.

About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide – including approximately 3.2 million people in the United States – and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

About Simeprevir
Simeprevir (TMC435) is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and its affiliated companies and Medivir AB for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the viral protease enzyme that enables the hepatitis C virus to replicate in host cells.

Janssen is responsible for the global clinical development of simeprevir and has acquired exclusive, worldwide marketing rights, except for the Nordic countries. Medivir AB will retain marketing rights for simeprevir in these Nordic countries under the marketing authorization held by Janssen-Cilag International NV.

On October 24, the U.S. Antiviral Drugs Advisory Committee of the FDA voted unanimously (19-0) to recommend approval of the new drug application filed by Janssen Research & Development, LLC for simeprevir administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C virus (HCV) in adult patients with compensated liver disease. Simeprevir was approved on September 27, 2013 in Japan for the treatment of genotype 1 hepatitis C. A Marketing Authorisation Application was submitted in April to the European Medicines Agency (EMA) by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C.

Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. To date, more than 43,700 patients have been treated with simeprevir in clinical trials.

In October, Janssen Pharmaceuticals, Inc. acquired the investigational compound GSK2336805, an NS5a replication complex inhibitor in phase II development for the treatment of chronic HCV, from an affiliate of GlaxoSmithKline plc. Since being acquired, the compound has been renamed JNJ-56914845. Janssen Pharmaceuticals plans to initiate phase II studies to evaluate the use of JNJ-56914845 in interferon-free combinations with simeprevir and TMC647055, the company’s non-nucleoside polymerase inhibitor, for the treatment of chronic HCV in adult patients with compensated liver disease.

About Sofosbuvir
Sofosbuvir (formerly referred to as GS-7977) is a once-daily nucleotide analog polymerase inhibitor for the treatment of HCV infection being developed by Gilead Sciences, Inc. Sofosbuvir is being evaluated as part of multiple therapeutic regimens, including programs with RBV alone and in combination with peg-IFN and RBV.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

Related:

Simeprevir + sofosbuvir produces high sustained response rates for hard-to-treat patients in COSMOS trial

By Liz Highleyman
Published: 05 November 2013
 
A 12-week all-oral combination of simeprevir plus sofosbuvir led to sustained virological response in 93% of genotype 1 prior null responders with mild-to-moderate liver fibrosis, working as well as a longer course of treatment or triple therapy including ribavirin, according to late-breaking findings from the COSMOS trial presented yesterday at 'The Liver Meeting 2013', the 64th annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC.
The study also showed that 100% of treatment-naive patients and null responders with advanced fibrosis or cirrhosis achieved early sustained response at 4 weeks post-treatment using the same dual regimen.

Continue Reading @ NAM


Saturday, November 2, 2013

AASLD-Janssen Will Present New Data For Simeprevir In Genotype 1 Hepatitis C Patients W-compensated Liver Disease

Simeprevir Administered Once Daily as Part of Combination Therapy Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Adult Patients 

Janssen announced today the presentation of new data for simeprevir in genotype 1 chronic hepatitis C patients with compensated liver disease at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC. These data include analyses of simeprevir in the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, including patients with the IL28B TT genotype and METAVIR scores of F4. This follows last week's unanimous vote by the FDA's Antiviral Drugs Advisory Committee to recommend approval of simeprevir.
 
Data from the Phase 2a COSMOS study of simeprevir administered once daily with Gilead's investigational nucleotide inhibitor sofosbuvir, with and without ribavirin, in genotype 1 chronic hepatitis C adult patients with compensated liver disease will also be presented during a late-breaking oral session on Monday, November 4.
 
Simeprevir Administered Once Daily as Part of Combination Therapy Demonstrates Sustained Virologic Response in Treatment-Naïve and Treatment-Experienced Genotype 1 Chronic Hepatitis C Adult Patients
 
WASHINGTON (Nov. 2, 2013) -- Janssen R&D Ireland (Janssen) today announced the presentation of new data at The Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Washington, DC for the investigational protease inhibitor simeprevir (TMC435) in the treatment of genotype 1 chronic hepatitis C in treatment-naïve and treatment-experienced adult patients with compensated liver disease. In analyses of the Phase 3 QUEST-1 and QUEST-2 studies in treatment-naïve patients and the Phase 3 PROMISE study in prior relapse patients, the efficacy of simeprevir was observed in hepatitis C patients, including patients with the IL28BTT genotype and METAVIR scores of F4.
 
"Patients with certain baseline characteristics can be more likely to fail or relapse after prior treatment," said Ira Jacobson, M.D., simeprevir clinical trial investigator, chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, Weill Cornell Medical College, and attending physician, New York-Presbyterian Hospital/Weill Cornell Medical Center. "The breadth of simeprevir data presented at AASLD reinforce its potential as a treatment option for patients and will offer important guidance to physicians once simeprevir is approved."
 
On October 24, the U.S. Antiviral Drugs Advisory Committee of the FDA voted unanimously (19-0) to recommend approval of the new drug application filed by Janssen Research & Development, LLC for simeprevir administered once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C virus (HCV) in adult patients with compensated liver disease.
 
Pooled Analysis from QUEST-1 and QUEST-2 Confirms Clinical Benefit of Simeprevir in Sub-Populations of Patients (Abstract 1122)
In a pooled analysis of the Phase 3 QUEST-1 and QUEST-2 studies, 80 percent of treatment-naïve patients treated with simeprevir in combination with pegylated interferon and ribavirin achieved the primary endpoint of sustained virologic response 12 weeks after the end of treatment (SVR12) compared to 50 percent of patients treated with placebo plus pegylated interferon and ribavirin. The pooled analysis found that 61 percent of patients with the IL28B TT genotype, 60 percent of patients with a METAVIR score of F4 and 75 percent of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 21 percent, 34 percent and 47 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively. Among patients with the genotype 1a Q80K polymorphism at baseline, 58 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 52 percent of patients treated with placebo in combination with pegylated interferon and ribavirin, but the difference was not statistically significant.
 
Eight percent and 10 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin experienced on-treatment failure and relapse, respectively, compared to 33 percent and 15 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively. Three percent of patients treated with simeprevir discontinued treatment early due to an adverse event compared to two percent of patients treated with placebo.
 
Analysis from PROMISE Reinforces Efficacy of Simeprevir in Sub-Populations of Patients (Abstract 1092)
In the pivotal Phase 3 PROMISE study, 79 percent of treatment-experienced hepatitis C patients treated with simeprevir in combination with pegylated interferon and ribavirin who previously experienced a relapse after prior treatment with pegylated interferon-based therapy achieved the primary endpoint of SVR12 compared to 37 percent of patients treated with placebo plus pegylated interferon and ribavirin. In this sub-analysis, 65 percent of patients with the IL28B TT genotype, 74 percent of patients with a METAVIR score of F4 and 70 percent of patients with genotype 1a HCV treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 19 percent, 26 percent and 28 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively.Among patients with the genotype 1a Q80K polymorphism at baseline, 47 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin achieved SVR12 compared to 30 percent of patients treated with placebo in combination with pegylated interferon and ribavirin.
 
The most common adverse events in patients treated with simeprevir combined with pegylated interferon and ribavirin in the first 12 weeks were fatigue, headache and influenza-like illness. Three percent and 18 percent of patients treated with simeprevir combined with pegylated interferon and ribavirin experienced on-treatment failure and relapse, respectively, compared to 27 percent and 34 percent of patients taking placebo plus pegylated interferon and ribavirin, respectively.
 
"We are very proud of the depth and breadth of our clinical trial program," said Gaston Picchio, Disease Area Leader Hepatitis, Janssen Research & Development. "Following last week's positive vote from the FDA's Antiviral Drugs Advisory Committee to recommend approval of simeprevir, we look forward to making simeprevir available to patients living with chronic HCV."
 
About Hepatitis C
Hepatitis C, a blood-borne infectious disease of the liver and a leading cause of chronic liver disease, is the focus of a rapidly evolving treatment landscape. Approximately 150 million people are infected with hepatitis C worldwide - including approximately 3.2 million people in the United States - and 350,000 people per year die from the disease globally. When left untreated, hepatitis C can cause significant damage to the liver including cirrhosis. Additionally, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.
 
About Simeprevir
Simeprevir (TMC435) is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and its affiliated companies and Medivir AB for the treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the viral protease enzyme that enables the hepatitis C virus to replicate in host cells.
 
Janssen is responsible for the global clinical development of simeprevir and has acquired exclusive, worldwide marketing rights, except for the Nordic countries. Medivir AB will retain marketing rights for simeprevir in these Nordic countries under the marketing authorization held by Janssen-Cilag International NV. Simeprevir was approved on September 27, 2013 in Japan for the treatment of genotype 1 hepatitis C and a Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C.
 
Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.
 
In October, Janssen Pharmaceuticals, Inc. acquired the investigational compound GSK2336805, an NS5a replication complex inhibitor in Phase 2 development for the treatment of chronic HCV, from an affiliate of GlaxoSmithKline plc. Since being acquired, the compound has been renamed JNJ-56914845. Janssen Pharmaceuticals plans to initiate Phase 2 studies to evaluate the use of JNJ-56914845 in interferon-free combinations with simeprevir and TMC647055, the company's non-nucleoside polymerase inhibitor, for the treatment of chronic HCV in adult patients with compensated liver disease.
 
For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.
 
About Janssen R&D Ireland
 
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen R&D Ireland is part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information. #
 
###
Craig Stoltz
Director, Product Communication
Global Pharmaceuticals Communication & Public Affairs
 
Janssen Global Services, LLC
Phone 609-730-2823
Fax 609-730-3770
Mobile 215-779-9396
cstoltz@its.jnj.com


Friday, November 1, 2013

Cocktails of new oral antiviral drugs to fight hepatitis C have aced clinical trials

Improved treatments offer hope for eradication of viral liver infection

Sara Reardon           


For decades, people with hepatitis C virus (HCV) have had to endure gruelling treatment regimens that include injections of the drug interferon, which can cause severe nausea and depression. But with the imminent approval of several highly effective oral antiviral drugs, and more on the way, researchers say that eradicating the infection worldwide is now a realistic goal.

Unlike previous HCV treatments, which sought to enhance the immune system with interferon and other drugs, the latest group of oral medications interferes with the virus's ability to replicate and make proteins. A US Food and Drug Administration (FDA) board recommended two such drugs - simeprevir, made by Johnson & Johnson in New Brunswick, New Jersey,  and sofosbuvir from Gilead Sciences in Foster City, California - for approval last week. When each is taken in combination with a drug called ribavirin, the treatment eliminates hepatitis C in around 80% of people.

"This is the first time in the history of humankind that we have a cure for a viral disease," says pharmacologist Raymond Schinazi of Emory University in Atlanta, Georgia.

Findings from trials of different drug combinations are set to be released this week. A phase II study called COSMOS tested a combination of sofosbuvir and simeprevir in 197 people with HCV who had either not responded to interferon or who had advanced liver fibrosis caused by the virus. After 12 weeks of treatment, the drugs completely cleared the virus in more than 90% of participants.

Another study, led by physician Kazuaki Chayama at Hiroshima University in Japan, treated 220 people with a combination of daclatasvir and asunaprevir, two new drugs from Bristol-Myers Squibb in New York. The cocktail cured 85% of participants. Eric Hughes, lead global medical researcher at the company, says that it plans to submit the drugs for FDA approval in 2014.
 
Stopped short
Despite such encouraging results, larger studies of drug combinations involving multiple drug companies seem to be unlikely. Charlotte Edenius, vice-president of development at Medivir, a drug company in Stockholm that collaborated with Johnson & Johnson on the COSMOS study, says that Gilead and Johnson & Johnson do not plan to work together for a phase III trial. Similarly, a Bristol-Myers Squibb spokesperson says the company has no plans to collaborate with Gilead on larger trials of a combined sofosbuvir daclatasvir therapy, despite a phase II trial completed earlier this year in which the drug pairing cured all 41 participants.

Even without phase III trials or FDA approval for this approach, David Thomas, a hepatitis C researcher at Johns Hopkins University in Baltimore, Maryland, expects that some physicians will begin prescribing such combinations 'off-label' for difficult-to-treat cases.

And, he says, the impressive cure rates achieved in clinical trials suggest that potent drug combinations could eradicate HCV worldwide - at least in theory. The virus does not have an animal reservoir, meaning that it is not harboured by other animals, and it is not easily spread between people, except through blood. Improved screening of blood supplies used for transfusions and better patient-screening techniques have already greatly cut transmission rates over the last 15 years. Emergence of drug-resistant virus strains could be a hurdle, adds Thomas, but they might be rare because the latest antiviral drugs are so potent in combination.
 
Price problem
Hepatologist Rajender Reddy at the University of Pennsylvania in Philadelphia sees a second stumbling block: getting such treatments to people who need them. Many of the roughly 170 million people worldwide who carry hepatitis C will not be able to afford the drugs, he says. There is also little incentive for drug companies to lower costs - unlike antiviral therapies for HIV, which must be taken for a patient's lifetime, HCV treatment is given for only 12 weeks. Identifying HCV carriers is also challenging, because most people do not know that they have the disease until they develop severe cirrhosis or liver cancer - sometimes decades after being infected.  Mandatory screening of at-risk populations such as the elderly and drug users would need to be a major part of an eradication effort, says virologist Charles Rice of Rockefeller University in New York. Crucial too is education to prevent people from contracting the disease in the first place. Even the most effective oral drugs do not raise a lasting immune response against the virus, and people can be reinfected. That is why the search for a preventative HCV vaccine continues, with the most promising ones currently in phase II clinical trials. "Even if we have all the drugs we need - which is still an open question - it will be decades, if not a century, before it's gone," says Rice.