Idenix, Janssen begin phase 2 study of all-oral DAA therapy for HCV
Idenix Pharmaceuticals and Janssen Pharmaceuticals have begun enrollment in a phase 2 clinical trial to evaluate an all-oral, direct-acting antiviral combination for treatment of hepatitis C, according to an Idenix news release.
The 12-week HELIX-2 trial will analyze response to a combined treatment of samatasvir, a pan-genotypic NS5A inhibitor from Idenix; simeprevir, an NS3/4A protease inhibitor from Janssen R&D Ireland and Medivir AB; and TMC647055, an NS5B non-nucleoside polymerase inhibitor from Janssen, the release said.
The randomized, open-label trial will study treatment-naive HCV patients, as well as those who have relapsed after treatment with ribavirin and interferon. Patients will receive 50 mg samatasvir, 75 mg simeprevir and 450 mg TMC647055 boosted by 30 mg ritonavir once daily for 12 weeks, with or without ribavirin.
The trial is the second as part of a collaboration agreement between Idenix and Janssen. The HELIX-1 trial studying samatasvir and simeprevir is ongoing, the release said.
“We are pleased with the continuing progress of our clinical program for samatasvir, which will provide additional important information on the use of this promising compound as part of all-oral HCV combination regimens,” Doug Mayers, MD, Idenix’s chief medical officer, said in the release. “With the advancement of the samatasvir program, as well as that of our novel nucleotide prodrug inhibitor, IDX21437, we anticipate initiating the evaluation of our own HCV combination regimen in 2014.”
http://www.healio.com/infectious-disease/hepatitis-resource-center-2013/idenix-janssen-begin-phase-2-study-of-all-oral-daa-therapy-for-hcv
An all-oral phase IIa study combining Simeprevir, TMC647055 and JNJ56914845 in hepatitis C patients to be initiated
Stockholm, Sweden—Medivir AB (OMX: MVIR), announces the initiation of a phase IIa trial in chronic genotype 1 hepatitis C infected patients to evaluate the efficacy, safety and tolerability of a 12-week combination therapy of simeprevir, TMC647055 and JNJ56914845, a NS5A replication complex inhibitor.
Study design
Approximately 40 patients will be enrolled in this open-label study to assess the efficacy, safety and tolerability of the co-administration of simeprevir, TMC647055 and two different doses of JNJ56914845 without ribavirin. The trial will evaluate genotype 1a and 1b HCV-infected patients who are either treatment-naïve or who have relapsed after prior treatment with interferon and ribavirin. Patients will receive 75 mg of simeprevir, 30 or 60 mg of JNJ56914845 and 450 mg of TMC647055 plus a low dose of ritonavir as a pharmacokinetic enhancer, each once daily for 12 weeks.
For additional information about this study, please visit www.clinicaltrials.gov
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 08.30 a.m. CET on 12 December 2013.
About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 & 4 infected patients with compensated liver disease, including cirrhosis.
Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan and in the USA and Canada in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.
About TMC647055
TMC647055 is a potent non-nucleoside hepatitis C polymerase inhibitor with broad genotypic coverage. TMC647055 is in phase II clinical development and is developed by Janssen R&D Ireland to treat chronic hepatitis C virus infections. TMC647055 is being investigated in combination with other DAA agents in all oral interferon-free regimens. There have been no treatment-emergent serious adverse events reported in the program.
About JNJ56914845
JNJ56914845, is a potent NS5A replication complex inhibitor. To date phase I and phase II clinical studies conducted demonstrated that JNJ56914845 60 mg once daily is well tolerated and produces rapid, substantial decreases in HCV RNA in treatment-naïve CHC subjects when given alone as a single dose and for 4 weeks in combination with pegIFN 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 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
Thursday, December 12, 2013
Listen To: Hepatitis-C: Millions at Risk
Posted Wednesday, December 11, 2013
Hepatitis C is a nasty disease that can lie dormant for years before attacking the liver. It's an emerging public health crisis: Five times more people have it than have HIV. It's such a crisis that the U.S. Preventive Services Task Force recommends every American born between 1945 and 1965 be tested. That's every baby boomer. Join Mike McIntyre for discussion about Hepatitis C, the push for testing and promising new treatments, Wednesday morning at 9:00 on The Sound of Ideas.
Listen below, or watch video
Pierre M. Gholam, MD, UH Case Medical Center, Division of Gastroenterology and Liver Disease
Melissa Osborn, MD, infectious disease specialist, MetroHealth System
Mary DiOrio, MD, Ohio State Epidemiologist
http://www.ideastream.org/soi/entry/58201
Wednesday, December 11, 2013
The Challenges of Caring for Newly Diagnosed Patients With HCV: Filling the Gap
The Challenges of Caring for Newly Diagnosed Patients With HCV: Filling the Gap
An Increasing Role for ID and Primary Care Clinicians?
Kaushal B. Shah, MD, Dawd S. Siraj, MD, MPH&TM
December 11, 2013
Hepatitis C Virus Infection
Hepatitis C virus (HCV) is an RNA virus causing major worldwide morbidity and mortality. If not diagnosed and treated early, HCV can have severe complications, including esophageal varices, liver cirrhosis with decompensation, and hepatocellular carcinoma. It is the leading indication for liver transplantation and a leading cause of hepatocellular carcinoma in the United States.[1]
Since the discovery of HCV in 1989,[2] remarkable progress has been made in its treatment. The newly approved direct-acting antiviral (DAA) protease inhibitor-based regimen has improved response rates, ushering in a new era in the management of patients with HCV. More effective, short course, and simpler regimens are expected in the near future. The recent update in the screening guidelines published by the US Preventive Services Task Force (USPSTF)[3] is expected to increase the number of patients seeking care.
Epidemiology of HCV
HCV infects 170-200 million people around the globe, accounting for 3% of world's population. It is a much bigger problem compared with HIV, which has an overall prevalence of only about 34 million.[4] In United States, approximately 3.2 million people are infected with HCV, and about two thirds are unaware of their diagnosis.[5]
HCV is the most common chronic bloodborne pathogen in the United States. HCV antibody prevalence approaches 1.6%, and 78% of persons who test positive have detectable viremia.[6]
Currently, 6 major genotypes and more than 80 subtypes have been identified worldwide.[7] Genotype 1 is the most common type in the United States,[8] where an estimated 16,000 new cases of HCV and 15,000 HCV-related deaths occur yearly.[3]
HCV Screening and Diagnosis
Screening Guidelines
In the United States, the most important risk factor for HCV infection remains injection drug use. Other risk factors include past or current injection drug use, receipt of a blood transfusion before 1992, being born to an HCV-infected mother, incarceration, intranasal drug use, unregulated tattoos, and other unregulated percutaneous exposures. Previous guidelines recommended risk-based screening.
Unfortunately, as many as 45% of all HCV diagnosed patients report no known exposure risk.[3] According to data from 1999 to 2008, about three fourths of patients in the United States living with HCV infection were born between 1945 and 1965, with a peak prevalence of 4.3% in persons aged 40-49 years.[3,9] After conducting 2 systematic reviews of the evidence on HCV progression, complications, and available therapies, in June 2013, the USPSTF updated the screening guidelines by adding 1-time HCV screening of people born between 1945 and 1965.[3]
With this change in the screening guideline, more than 800,000 people with chronic HCV will be identified.[10] This will undoubtedly stress the already stretched field of HCV clinicians. By the end of 2007, only 21% of all estimated infected persons had received antiviral therapy. If this trend is not changed, it is projected that only 14.5% of liver-related deaths related to HCV during 2002-2030 would be prevented.[11,12]
The reasons for these distressing statistics are multifactorial, with the lack of early screening with advanced disease at time of care and the limited number of specialists who treat patients with HCV being the main driving factors. The recently updated screening guideline is expected to improve this situation, but without a massive increase in HCV providers who will absorb the increased demand for care, its impact will be blunted.
Diagnostic Testing
For years, HCV treatment decisions have been based on stage of liver inflammation and fibrosis as determined by liver biopsy. Although considered the gold standard, liver biopsy is an invasive and expensive procedure that can be associated with morbidity and, rarely, mortality.[13] Furthermore, this test is saddled by significant sampling error (30%-35%), poor and inadequate sampling, and inter- and intrareader variability of interpretation of results.[13]
Noninvasive blood tests and ultrasonographic scanning of the liver are becoming increasingly precise in staging liver disease in patients with HCV.[14] The US Food and Drug Administration (FDA) approved liver ultrasonographic elastography, the FibroScan® (Echosens, Paris, France), in mid-2013. In a recent meta-analysis, the sensitivity and specificity of FibroScan to detect fibrosis were 87% and 91%, respectively.[15]
Paradigm Shift in Management of HCV
The main goal in the treatment of HCV is sustained virologic response (SVR). SVR is associated with a substantial (> 50%) reduction in risk for all-cause mortality[16] and substantially lower rates of liver-related death and decompensated cirrhosis with ascites, variceal bleeding, encephalopathy, or impaired hepatic synthetic function.[17]
In 2011, the first DAAs -- telaprevir and boceprevir -- were licensed in the United States for treatment of HCV genotype 1.[18,19] The addition of DAAs to the management of HCV has improved the rates of SVR from 44% to 75%.[20] Furthermore, approximately 20 new HCV treatments are undergoing phase 2 or phase 3 clinical trials.[21] These new regimens have improved side-effect profiles and are expected to improve SVR rates and shorten the duration of therapy.
Increased Demand for HIV Care
Currently, clinical HCV care is primarily provided by hepatologists and gastroenterologists. When screening was limited and rates of SVR were low, most patients with HCV sought medical attention late in the disease process, when they required advanced specialist care. Moreover, the need for liver biopsy to stage disease has centered the care of patients with HCV among hepatologists. The changing guidelines for screening, the precision of noninvasive techniques for staging liver disease, and the approval of highly effective DAAs will probably change this paradigm gradually.
In the United States, there are approximately 14,000 practicing gastroenterologists.[21] With no increase in fellowship positions, the surge in the HCV patient population will be an extraordinary burden on these already stretched HCV care providers. Furthermore, the multiple new drug combinations, complex drug/drug interactions and side-effect profiles, challenging socioeconomic issues, and comorbid conditions common in patients with HCV will require specialists who are familiar and comfortable with handling those complex issues.
There are many persuasive reasons for infectious diseases (ID) specialists to integrate HCV care into their practices. An estimated 15%-20% of patients with HIV are coinfected with HCV.[22] In HIV practice, we formulate complex antiviral combinations, manage drug/drug interactions of fundamentally similar medications to the HCV regimen (protease inhibitors, nucleosides, non-nucleosides), interpret results of antiviral drug resistance testing, and devise salvage regimens. ID specialists care for patients with HIV who have complex social, financial, substance abuse, alcoholism, depression, and nonadherence issues that require sustained and involved long-term care. Experience with the same general principles would apply and serve us well if we gradually incorporate care of HCV-infected patients into our practice.
HCV, like HIV, is a public health issue that requires an integrated approach to care. The focus on risk factor identification, diagnosis, transmission prevention, education, and provision of access to care will require clinicians to work closely with public health systems. ID specialists can apply their expertise in this area to help patients with HCV and strengthen the public health system.
The needs and care of patients with HIV and HCV are similar, but at the same time, ID specialists must appreciate the differences and create working relationships with hepatologists,
gastroenterologists, and transplant centers for more coordinated and effective care. This will foster a better transition of patient care when diagnostic and therapeutic services for such issues as variceal bleeding, ascites, hepatocellular carcinoma, or liver transplant are required.
With these issues in mind, the Infectious Diseases Society of America (IDSA) has created an HCV task force that is spearheading the training of ID physicians through increasing coverage at society meetings, preparing training webinars, and working on a curriculum for ID fellowship training in HCV patient care. In the long run, this will fill a crucial gap in the overall care of patients with HCV.[23]
If HCV screening is implemented as recommended and the number of patients increases as anticipated, the addition of ID clinicians might not even be adequate to meet the demand. The reasons and rationale that justify the need for ID physicians could work as well for primary care physicians, internists, and family medicine specialists. With proper training, the fundamental changes on evaluation and management of HCV will make it possible for these primary care providers to be involved in direct care of patients with HCV.
Clinic Organization for HCV Care
Clinicians who are planning to add HCV care to their practices will need a clinic-wide plan to prepare for the increased patient load and work volume.[24,25] Because staff resources and time are limited, healthcare providers will have to determine how best to allocate clinic resources and use support staff to maximize productivity without compromising the quality and safety of care. This is better handled if care is centered around a designated management team who will dedicate a portion of their time to HCV care.
Before offering the service and on an ongoing basis, the HCV management team should receive education on HCV and the current approved management of HCV. The complex drug/drug interaction profile, side effects, and dosing schedules make this education critical to providing quality standardized care. It would be advisable to prepare a manual or protocol to standardize knowledge and care among clinic staff.
Nurse practitioners, physician assistants, and pharmacists can be an integral part of the HCV management team. With proper supervision and education, they can play critical roles in the day-to-day care and follow-up of patients. Most of the issues that are brought by patients while undergoing HCV treatment can be addressed by these medical professionals, allowing physicians to use their time to evaluate new patients.
A New Era in HCV Care
A new era is dawning in HCV care. Multiple recent developments are playing a role in this change, including:
• Recent updates in the HCV screening guideline, which are expected to bring an unprecedented number of new patients;
• The approval of the FibroScan® and refinement of biochemical tests to noninvasively stage liver disease; and
• The approval of shorter, safer, more effective, and possibly all-oral DAA-based HCV treatment regimens.
As a result of these changes, not only we will see an increased number of patients who will be seeking care, but most will be at the early stage of their disease, further reducing the need for highly specialized tests and care. To meet this increased demand, more HCV care providers will be required in the near future. Considering their expertise in comprehensive HIV care, we believe that ID physicians are the ideal candidates to fill this critical gap. Collaborative training with hepatologists, modification of ID fellowship training to include HCV patient care, and multimedia continuous training of ID physicians by IDSA and the HCV task force should continue to pave the way for the new era.
http://www.medscape.com/viewarticle/815387_1
An Increasing Role for ID and Primary Care Clinicians?
Kaushal B. Shah, MD, Dawd S. Siraj, MD, MPH&TM
December 11, 2013
Hepatitis C Virus Infection
Hepatitis C virus (HCV) is an RNA virus causing major worldwide morbidity and mortality. If not diagnosed and treated early, HCV can have severe complications, including esophageal varices, liver cirrhosis with decompensation, and hepatocellular carcinoma. It is the leading indication for liver transplantation and a leading cause of hepatocellular carcinoma in the United States.[1]
Since the discovery of HCV in 1989,[2] remarkable progress has been made in its treatment. The newly approved direct-acting antiviral (DAA) protease inhibitor-based regimen has improved response rates, ushering in a new era in the management of patients with HCV. More effective, short course, and simpler regimens are expected in the near future. The recent update in the screening guidelines published by the US Preventive Services Task Force (USPSTF)[3] is expected to increase the number of patients seeking care.
Epidemiology of HCV
HCV infects 170-200 million people around the globe, accounting for 3% of world's population. It is a much bigger problem compared with HIV, which has an overall prevalence of only about 34 million.[4] In United States, approximately 3.2 million people are infected with HCV, and about two thirds are unaware of their diagnosis.[5]
HCV is the most common chronic bloodborne pathogen in the United States. HCV antibody prevalence approaches 1.6%, and 78% of persons who test positive have detectable viremia.[6]
Currently, 6 major genotypes and more than 80 subtypes have been identified worldwide.[7] Genotype 1 is the most common type in the United States,[8] where an estimated 16,000 new cases of HCV and 15,000 HCV-related deaths occur yearly.[3]
HCV Screening and Diagnosis
Screening Guidelines
In the United States, the most important risk factor for HCV infection remains injection drug use. Other risk factors include past or current injection drug use, receipt of a blood transfusion before 1992, being born to an HCV-infected mother, incarceration, intranasal drug use, unregulated tattoos, and other unregulated percutaneous exposures. Previous guidelines recommended risk-based screening.
Unfortunately, as many as 45% of all HCV diagnosed patients report no known exposure risk.[3] According to data from 1999 to 2008, about three fourths of patients in the United States living with HCV infection were born between 1945 and 1965, with a peak prevalence of 4.3% in persons aged 40-49 years.[3,9] After conducting 2 systematic reviews of the evidence on HCV progression, complications, and available therapies, in June 2013, the USPSTF updated the screening guidelines by adding 1-time HCV screening of people born between 1945 and 1965.[3]
With this change in the screening guideline, more than 800,000 people with chronic HCV will be identified.[10] This will undoubtedly stress the already stretched field of HCV clinicians. By the end of 2007, only 21% of all estimated infected persons had received antiviral therapy. If this trend is not changed, it is projected that only 14.5% of liver-related deaths related to HCV during 2002-2030 would be prevented.[11,12]
The reasons for these distressing statistics are multifactorial, with the lack of early screening with advanced disease at time of care and the limited number of specialists who treat patients with HCV being the main driving factors. The recently updated screening guideline is expected to improve this situation, but without a massive increase in HCV providers who will absorb the increased demand for care, its impact will be blunted.
Diagnostic Testing
For years, HCV treatment decisions have been based on stage of liver inflammation and fibrosis as determined by liver biopsy. Although considered the gold standard, liver biopsy is an invasive and expensive procedure that can be associated with morbidity and, rarely, mortality.[13] Furthermore, this test is saddled by significant sampling error (30%-35%), poor and inadequate sampling, and inter- and intrareader variability of interpretation of results.[13]
Noninvasive blood tests and ultrasonographic scanning of the liver are becoming increasingly precise in staging liver disease in patients with HCV.[14] The US Food and Drug Administration (FDA) approved liver ultrasonographic elastography, the FibroScan® (Echosens, Paris, France), in mid-2013. In a recent meta-analysis, the sensitivity and specificity of FibroScan to detect fibrosis were 87% and 91%, respectively.[15]
Paradigm Shift in Management of HCV
The main goal in the treatment of HCV is sustained virologic response (SVR). SVR is associated with a substantial (> 50%) reduction in risk for all-cause mortality[16] and substantially lower rates of liver-related death and decompensated cirrhosis with ascites, variceal bleeding, encephalopathy, or impaired hepatic synthetic function.[17]
In 2011, the first DAAs -- telaprevir and boceprevir -- were licensed in the United States for treatment of HCV genotype 1.[18,19] The addition of DAAs to the management of HCV has improved the rates of SVR from 44% to 75%.[20] Furthermore, approximately 20 new HCV treatments are undergoing phase 2 or phase 3 clinical trials.[21] These new regimens have improved side-effect profiles and are expected to improve SVR rates and shorten the duration of therapy.
Increased Demand for HIV Care
Currently, clinical HCV care is primarily provided by hepatologists and gastroenterologists. When screening was limited and rates of SVR were low, most patients with HCV sought medical attention late in the disease process, when they required advanced specialist care. Moreover, the need for liver biopsy to stage disease has centered the care of patients with HCV among hepatologists. The changing guidelines for screening, the precision of noninvasive techniques for staging liver disease, and the approval of highly effective DAAs will probably change this paradigm gradually.
In the United States, there are approximately 14,000 practicing gastroenterologists.[21] With no increase in fellowship positions, the surge in the HCV patient population will be an extraordinary burden on these already stretched HCV care providers. Furthermore, the multiple new drug combinations, complex drug/drug interactions and side-effect profiles, challenging socioeconomic issues, and comorbid conditions common in patients with HCV will require specialists who are familiar and comfortable with handling those complex issues.
There are many persuasive reasons for infectious diseases (ID) specialists to integrate HCV care into their practices. An estimated 15%-20% of patients with HIV are coinfected with HCV.[22] In HIV practice, we formulate complex antiviral combinations, manage drug/drug interactions of fundamentally similar medications to the HCV regimen (protease inhibitors, nucleosides, non-nucleosides), interpret results of antiviral drug resistance testing, and devise salvage regimens. ID specialists care for patients with HIV who have complex social, financial, substance abuse, alcoholism, depression, and nonadherence issues that require sustained and involved long-term care. Experience with the same general principles would apply and serve us well if we gradually incorporate care of HCV-infected patients into our practice.
HCV, like HIV, is a public health issue that requires an integrated approach to care. The focus on risk factor identification, diagnosis, transmission prevention, education, and provision of access to care will require clinicians to work closely with public health systems. ID specialists can apply their expertise in this area to help patients with HCV and strengthen the public health system.
The needs and care of patients with HIV and HCV are similar, but at the same time, ID specialists must appreciate the differences and create working relationships with hepatologists,
gastroenterologists, and transplant centers for more coordinated and effective care. This will foster a better transition of patient care when diagnostic and therapeutic services for such issues as variceal bleeding, ascites, hepatocellular carcinoma, or liver transplant are required.
With these issues in mind, the Infectious Diseases Society of America (IDSA) has created an HCV task force that is spearheading the training of ID physicians through increasing coverage at society meetings, preparing training webinars, and working on a curriculum for ID fellowship training in HCV patient care. In the long run, this will fill a crucial gap in the overall care of patients with HCV.[23]
If HCV screening is implemented as recommended and the number of patients increases as anticipated, the addition of ID clinicians might not even be adequate to meet the demand. The reasons and rationale that justify the need for ID physicians could work as well for primary care physicians, internists, and family medicine specialists. With proper training, the fundamental changes on evaluation and management of HCV will make it possible for these primary care providers to be involved in direct care of patients with HCV.
Clinic Organization for HCV Care
Clinicians who are planning to add HCV care to their practices will need a clinic-wide plan to prepare for the increased patient load and work volume.[24,25] Because staff resources and time are limited, healthcare providers will have to determine how best to allocate clinic resources and use support staff to maximize productivity without compromising the quality and safety of care. This is better handled if care is centered around a designated management team who will dedicate a portion of their time to HCV care.
Before offering the service and on an ongoing basis, the HCV management team should receive education on HCV and the current approved management of HCV. The complex drug/drug interaction profile, side effects, and dosing schedules make this education critical to providing quality standardized care. It would be advisable to prepare a manual or protocol to standardize knowledge and care among clinic staff.
Nurse practitioners, physician assistants, and pharmacists can be an integral part of the HCV management team. With proper supervision and education, they can play critical roles in the day-to-day care and follow-up of patients. Most of the issues that are brought by patients while undergoing HCV treatment can be addressed by these medical professionals, allowing physicians to use their time to evaluate new patients.
A New Era in HCV Care
A new era is dawning in HCV care. Multiple recent developments are playing a role in this change, including:
• Recent updates in the HCV screening guideline, which are expected to bring an unprecedented number of new patients;
• The approval of the FibroScan® and refinement of biochemical tests to noninvasively stage liver disease; and
• The approval of shorter, safer, more effective, and possibly all-oral DAA-based HCV treatment regimens.
As a result of these changes, not only we will see an increased number of patients who will be seeking care, but most will be at the early stage of their disease, further reducing the need for highly specialized tests and care. To meet this increased demand, more HCV care providers will be required in the near future. Considering their expertise in comprehensive HIV care, we believe that ID physicians are the ideal candidates to fill this critical gap. Collaborative training with hepatologists, modification of ID fellowship training to include HCV patient care, and multimedia continuous training of ID physicians by IDSA and the HCV task force should continue to pave the way for the new era.
http://www.medscape.com/viewarticle/815387_1
Diabetes Identified as Risk Factor for Liver Cancer Across Ethnic Groups
Diabetes Identified as Risk Factor for Liver Cancer Across Ethnic Groups
ATLANTA — Diabetes was associated with an increased risk for developing a type of liver cancer called hepatocellular carcinoma, and this association was highest for Latinos, followed by Hawaiians, African-Americans, and Japanese-Americans, according to results presented here at the Sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Dec. 6-9.
“People with diabetes have a two- to threefold higher risk for hepatocellular carcinoma compared with those without diabetes,” said V. Wendy Setiawan, Ph.D., assistant professor in the Department of Preventive Medicine at Keck School of Medicine of the University of Southern California. “We also found that the interethnic differences in the prevalence of diabetes were consistent with the pattern of hepatocellular carcinoma incidence observed across ethnicities: Ethnic groups with a high prevalence of diabetes also have high hepatocellular carcinoma rates, and those with a lower prevalence of diabetes have lower hepatocellular carcinoma rates.”
The number of new cases of hepatocellular carcinoma in the United States tripled in the past three decades, with Latinos and African-Americans experiencing the largest increase in incidence. Prior research has suggested that diabetes may be a risk factor for hepatocellular carcinoma, and its increasing incidence may be contributing to the rising rate of hepatocellular carcinoma.
“People with diabetes should be aware that their condition is associated with a higher risk of developing hepatocellular carcinoma,” Setiawan said. “Maintaining a healthy weight, managing their diabetes, preventing and treating hepatitis infection, and limiting alcohol and tobacco use should be in their priority to-do list.”
In addition, Setiawan said that public health efforts encouraging obesity/diabetes prevention and effective diabetes management should be directed at high-risk populations.
Setiawan and colleagues examined if the association between diabetes and hepatocellular carcinoma differed by race/ethnic group. They analyzed data from more than 150,000 people enrolled in the Multiethnic Cohort Study between 1993 and 1996. During the study follow-up period of about 15 years, 506 cases of hepatocellular carcinoma were reported: 59 cases in non-Hispanic whites, 81 in African-Americans, 33 in Hawaiians, 158 in Japanese-Americans, and 175 in Latinos.
Compared with non-Hispanic whites, Latinos had 2.77 times the risk for being diagnosed with hepatocellular carcinoma, the highest risk identified. Native Hawaiians had 2.48 times the risk; African-Americans, 2.16; and Japanese-Americans, 2.07.
The prevalence of diabetes was consistent with that of hepatocellular carcinoma. Sixteen percent of Hawaiians, 15 percent of Latinos and African-Americans, 10 percent of Japanese-Americans, and 6 percent of non-Hispanic whites had diabetes. Compared with those without diabetes, Latinos with diabetes had 3.3-fold higher risk for hepatocellular carcinoma; Hawaiians, 2.33-fold higher risk; Japanese-Americans, 2.02-fold higher risk; African-Americans, 2.02-fold higher risk; and non-Hispanic whites had 2.17-fold higher risk.
Hepatocellular carcinoma was attributed to diabetes in 26 percent of cases in Latinos, 20 percent of Hawaiians, 13 percent of African-Americans, 12 percent of Japanese-Americans, and 6 percent of non-Hispanic whites, the researchers estimated. According to Setiawan, eliminating diabetes could potentially reduce hepatocellular carcinoma incidence in all racial/ethnic groups, with the largest potential reduction possible in Latinos.
This study was funded by the National Cancer Institute. Setiawan has declared no conflicts of interest.
ATLANTA — Diabetes was associated with an increased risk for developing a type of liver cancer called hepatocellular carcinoma, and this association was highest for Latinos, followed by Hawaiians, African-Americans, and Japanese-Americans, according to results presented here at the Sixth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved, held Dec. 6-9.
“People with diabetes have a two- to threefold higher risk for hepatocellular carcinoma compared with those without diabetes,” said V. Wendy Setiawan, Ph.D., assistant professor in the Department of Preventive Medicine at Keck School of Medicine of the University of Southern California. “We also found that the interethnic differences in the prevalence of diabetes were consistent with the pattern of hepatocellular carcinoma incidence observed across ethnicities: Ethnic groups with a high prevalence of diabetes also have high hepatocellular carcinoma rates, and those with a lower prevalence of diabetes have lower hepatocellular carcinoma rates.”
The number of new cases of hepatocellular carcinoma in the United States tripled in the past three decades, with Latinos and African-Americans experiencing the largest increase in incidence. Prior research has suggested that diabetes may be a risk factor for hepatocellular carcinoma, and its increasing incidence may be contributing to the rising rate of hepatocellular carcinoma.
“People with diabetes should be aware that their condition is associated with a higher risk of developing hepatocellular carcinoma,” Setiawan said. “Maintaining a healthy weight, managing their diabetes, preventing and treating hepatitis infection, and limiting alcohol and tobacco use should be in their priority to-do list.”
In addition, Setiawan said that public health efforts encouraging obesity/diabetes prevention and effective diabetes management should be directed at high-risk populations.
Setiawan and colleagues examined if the association between diabetes and hepatocellular carcinoma differed by race/ethnic group. They analyzed data from more than 150,000 people enrolled in the Multiethnic Cohort Study between 1993 and 1996. During the study follow-up period of about 15 years, 506 cases of hepatocellular carcinoma were reported: 59 cases in non-Hispanic whites, 81 in African-Americans, 33 in Hawaiians, 158 in Japanese-Americans, and 175 in Latinos.
Compared with non-Hispanic whites, Latinos had 2.77 times the risk for being diagnosed with hepatocellular carcinoma, the highest risk identified. Native Hawaiians had 2.48 times the risk; African-Americans, 2.16; and Japanese-Americans, 2.07.
The prevalence of diabetes was consistent with that of hepatocellular carcinoma. Sixteen percent of Hawaiians, 15 percent of Latinos and African-Americans, 10 percent of Japanese-Americans, and 6 percent of non-Hispanic whites had diabetes. Compared with those without diabetes, Latinos with diabetes had 3.3-fold higher risk for hepatocellular carcinoma; Hawaiians, 2.33-fold higher risk; Japanese-Americans, 2.02-fold higher risk; African-Americans, 2.02-fold higher risk; and non-Hispanic whites had 2.17-fold higher risk.
Hepatocellular carcinoma was attributed to diabetes in 26 percent of cases in Latinos, 20 percent of Hawaiians, 13 percent of African-Americans, 12 percent of Japanese-Americans, and 6 percent of non-Hispanic whites, the researchers estimated. According to Setiawan, eliminating diabetes could potentially reduce hepatocellular carcinoma incidence in all racial/ethnic groups, with the largest potential reduction possible in Latinos.
This study was funded by the National Cancer Institute. Setiawan has declared no conflicts of interest.
Best treatment options for HCV genotype 1: All of them contain sofosbuvir, all are expensive
December 8th, 2013
HIV and ID Observations
Simeprevir and (Especially) Sofosbuvir Are Great Leaps Forward — and They Will Cost Plenty
Paul E. Sax, MD
Hepatitis C has been potentially curable for decades, but it’s hardly been easy. “I feel like I’m slowly killing myself,” said one of my patients, memorably, during week 24 of a planned bazillion-week course of interferon-ribavirin. (Actually it was only 48 weeks, but seemed like a bazillion weeks.)
Then in 2011 came the addition of telaprevir or boceprevir to the interferon-ribavirin, which made a cure more likely, but the treatment even worse. Rashes. Need for fatty meals. Tons of pills. Taste disturbance. Anal discomfort. (“Like shitting glass,” another memorable quote.) Anemia. And for the providers, having to manage these side effects and the complex “response-guided therapy” algorithms was no picnic.
Now, with the approval of simeprevir in November and in particular sofosbuvir Friday, HCV cure just got a whole lot easier. Both are one pill a day. Both have far fewer side effects than any existing HCV drug. Sofosbuvir adds the benefit of having almost zero important drug-drug interactions. (Simeprevir has many.)
The main problem with these new treatments is, frankly, their cost. They are very expensive — 12 weeks of simeprevir will be $65,000, of sofosbuvir $80,000. These costs are offset somewhat by reduced need for monitoring with safer therapies, a shorter course of interferon and ribavirin (if you go that route), and presumably down the road, prevented cases of cirrhosis, hepatocellular carcinoma, and liver transplantation.
And of course, few individuals will actually pay full price out of pocket for these treatments, just like few actually pay for their MRIs or their angioplasties or their stay in the ICU. Treating HCV is not like cosmetic surgery; it’s potentially lifesaving. And as with other expensive but lifesaving treatments, we’re hoping there will be generous patient-assistance programs for those who can’t pay.
But for those without coverage, people in other countries, or those charged with managing pharmacy budgets, this cost is a major hurdle.
All of which leaves me thinking that as of December 8, 2013, these are the best options for genotype 1 HCV infection (cost estimates approximate):
1. Simeprevir + sofosbuvir for 12 weeks.
PROS: More than 90% cure rate in the COSMOS study.
Two pills once daily (it’s amazing even to write that.)
CONS: The COSMOS study was very small. Simeprevir can lead to photosensitivity and has many drug-drug interactions. The Q80K polymorphism may reduce response to simeprevir.
This regimen is not “FDA approved.” Cost = $145,000.
2. Sofosbuvir + ribavirin for 24 weeks.
PROS: Cured 76% of HIV/HCV co-infected patients in the PHOTON-1 study. May well do better in HCV mono-infected. Regimen is “FDA approved” for interferon-ineligible patients, which could help get insurance coverage.
CONS. Ribavirin, and all its side effects. 24 weeks seems long compared to 12 weeks. Response rate is lower than other options listed here, which would require re-treatment.
Cost (not including ribavirin) = $160,000.
3. Sofosbuvir + interferon + ribavirin for 12 weeks:
PROS: 90% cure rate in the NEUTRINO study. Only 12 weeks of interferon and ribavirin.
Cost = $90,000. CONS: Interferon. Ribavirin. Enough said.
All are a lot better than what we had just last week. All of them contain sofosbuvir. And all are expensive.
Read More At - http://blogs.jwatch.org/hiv-id-observations/index.php/simeprevir-and-especially-sofosbuvir-are-great-leaps-forward-and-they-will-cost-plenty/2013/12/08/
HIV and ID Observations
Simeprevir and (Especially) Sofosbuvir Are Great Leaps Forward — and They Will Cost Plenty
Paul E. Sax, MD
Hepatitis C has been potentially curable for decades, but it’s hardly been easy. “I feel like I’m slowly killing myself,” said one of my patients, memorably, during week 24 of a planned bazillion-week course of interferon-ribavirin. (Actually it was only 48 weeks, but seemed like a bazillion weeks.)
Then in 2011 came the addition of telaprevir or boceprevir to the interferon-ribavirin, which made a cure more likely, but the treatment even worse. Rashes. Need for fatty meals. Tons of pills. Taste disturbance. Anal discomfort. (“Like shitting glass,” another memorable quote.) Anemia. And for the providers, having to manage these side effects and the complex “response-guided therapy” algorithms was no picnic.
Now, with the approval of simeprevir in November and in particular sofosbuvir Friday, HCV cure just got a whole lot easier. Both are one pill a day. Both have far fewer side effects than any existing HCV drug. Sofosbuvir adds the benefit of having almost zero important drug-drug interactions. (Simeprevir has many.)
The main problem with these new treatments is, frankly, their cost. They are very expensive — 12 weeks of simeprevir will be $65,000, of sofosbuvir $80,000. These costs are offset somewhat by reduced need for monitoring with safer therapies, a shorter course of interferon and ribavirin (if you go that route), and presumably down the road, prevented cases of cirrhosis, hepatocellular carcinoma, and liver transplantation.
And of course, few individuals will actually pay full price out of pocket for these treatments, just like few actually pay for their MRIs or their angioplasties or their stay in the ICU. Treating HCV is not like cosmetic surgery; it’s potentially lifesaving. And as with other expensive but lifesaving treatments, we’re hoping there will be generous patient-assistance programs for those who can’t pay.
But for those without coverage, people in other countries, or those charged with managing pharmacy budgets, this cost is a major hurdle.
All of which leaves me thinking that as of December 8, 2013, these are the best options for genotype 1 HCV infection (cost estimates approximate):
1. Simeprevir + sofosbuvir for 12 weeks.
PROS: More than 90% cure rate in the COSMOS study.
Two pills once daily (it’s amazing even to write that.)
CONS: The COSMOS study was very small. Simeprevir can lead to photosensitivity and has many drug-drug interactions. The Q80K polymorphism may reduce response to simeprevir.
This regimen is not “FDA approved.” Cost = $145,000.
2. Sofosbuvir + ribavirin for 24 weeks.
PROS: Cured 76% of HIV/HCV co-infected patients in the PHOTON-1 study. May well do better in HCV mono-infected. Regimen is “FDA approved” for interferon-ineligible patients, which could help get insurance coverage.
CONS. Ribavirin, and all its side effects. 24 weeks seems long compared to 12 weeks. Response rate is lower than other options listed here, which would require re-treatment.
Cost (not including ribavirin) = $160,000.
3. Sofosbuvir + interferon + ribavirin for 12 weeks:
PROS: 90% cure rate in the NEUTRINO study. Only 12 weeks of interferon and ribavirin.
Cost = $90,000. CONS: Interferon. Ribavirin. Enough said.
All are a lot better than what we had just last week. All of them contain sofosbuvir. And all are expensive.
Read More At - http://blogs.jwatch.org/hiv-id-observations/index.php/simeprevir-and-especially-sofosbuvir-are-great-leaps-forward-and-they-will-cost-plenty/2013/12/08/
Transcript HCV Drugs - Achillion and Idenix presents at Oppenheimer 24th Annual Healthcare Conference
Hello folks,
Both, Achillion and Idenix presented at Oppenheimer 24th Annual Healthcare Conference, transcripts are available over at Seeking Alpha , below is an excerpt from each presentation.
*Free registration may be required
Achillion Pharmaceuticals, Inc. (ACHN) Oppenheimer 24th Annual Healthcare Conference
Transcript December 11, 2013 1:35 PM ET
View full transcript @ Seeking Alpha
Continue reading...
Idenix Pharmaceuticals, Inc. at Oppenheimer 24th Annual Healthcare Conference (Transcript)
Continue reading..
Source - http://seekingalpha.com/
Both, Achillion and Idenix presented at Oppenheimer 24th Annual Healthcare Conference, transcripts are available over at Seeking Alpha , below is an excerpt from each presentation.
*Free registration may be required
Achillion Pharmaceuticals, Inc. (ACHN) Oppenheimer 24th Annual Healthcare Conference
Transcript December 11, 2013 1:35 PM ET
View full transcript @ Seeking Alpha
So digging a little deeper into the individual characteristics of the compound in the portfolio, I will start out with ACH-3422 which is the NS5B polymerase inhibitor. For the overall characteristics of ACH-3422, this compound is a novel nucleotide prodrug of a uridine analog and there are certain advantages for selecting a uridine analog over say [Indiscernible] analog. These are advantages come not only in terms of safety but also the high efficacy that is associated with uridine analog.
3422 is highly specific for inhibition of HCV polymerase. It does not inhibit any of the human DNA or RNA polymerase. It is potent and specific for hepatitis C and has demonstrated pan-genotypic activity and a high barrier to resistance as one would anticipate with a nucleotide prodrug. In terms of the pharmacokinetic and metabolism of 3422, we see rapid conversion of prodrug to the monophosphate in microsomes as well as in hepatocytes. The half life of the triphosphate that is generated is/are greater than 24 hours indicating that the drug has potentials for once daily dosing for the preclinical studies that we have done so far. We have completed 14 days safety studies. We have obtained high exposures of the triphosphate in the liver in these studies and so far all the non-clinical data that we have supports our continued development into the clinic.
If we compare the potency of ACH-3422 to Sofosbuvir across different genotypes, what we see is that the potency of 3422 is at least comparable to or better than the potency of Sofosbuvir. We have compared the potency in genotypes 1a, genotype 2, genotype 3 and genotype 4 and especially in genotype 3, we see a significant improvement in the potency of 3422 as compared to Sofosbuvir.
Continue reading...
Idenix Pharmaceuticals, Inc. at Oppenheimer 24th Annual Healthcare Conference (Transcript)
So, going directly to our lead nucleotide prodrug candidate – this is IDX21437. This is a next generation uridine nucleotide prodrug currently in phase one to clinical testing. This trail has started in Canada. We announced this I think a little over a month ago. And this is a compound that in vitro has demonstrated potent Pangenous [ph] activity. And that we seen very impressive – liver triphosphate levels generated in dibo.
So, this gives us some confidence that in the human, in the clinical trial – we’ll see nice anti-viral activity. We’ll need to see the data before we can draw any hard conclusions on that but at least we like what we see pre-clinically at this point.
And, really, that was the basic for discussions around the collaboration with Johnson pharmaceutical around our Helix One and Helix Two combination drug acting in our viral trials.
So, a little bit about those trials. This is the collaboration with J&J, it’s a non-exclusive HCV collaboration. Helix One is about putting two drugs together. So, our NS5A, inhibitor, Samatasvir and their pro-agent inhibitor’s recently been approved but the generic name for this, simeprevir, and then Helix Two is about putting three drugs together – which is Samatasvir, simprevir and then they have a ritonavir boosted non-nucleotide inhibitor which I’ll just call O55, it’s got a long name, but we’ll just call it O55 for now.
Continue reading..
Source - http://seekingalpha.com/
Why Talk Of A Hepatitis C Price War Should Act As A Warning To The Pharma Industry-At-Large
Why Talk Of A Hepatitis C Price War Should Act As A Warning To The Pharma Industry-At-Large
Simon King, Contributor
Bloomberg Bloomberg reporter Drew Armstrong may have broken one of the most important pharmaceutical news stories of the year on Tuesday when he revealed that a leading US pharmacy benefits manager (PBM) is to take an aggressive stance towards the pricing of new hepatitis C therapies.
The crux of the story is that Express Scripts ESRX -0.58% will not view the convenience of Gilead Sciences' GILD -2.11% proposed single-tablet, fixed-dose combination treatment – due to be approved in late 2014/early 2015 – as an adequate justification for higher pricing versus less convenient therapies (i.e. more tablets) that deliverer a similar level of efficacy.
Continue reading...
Simon King, Contributor
Bloomberg Bloomberg reporter Drew Armstrong may have broken one of the most important pharmaceutical news stories of the year on Tuesday when he revealed that a leading US pharmacy benefits manager (PBM) is to take an aggressive stance towards the pricing of new hepatitis C therapies.
The crux of the story is that Express Scripts ESRX -0.58% will not view the convenience of Gilead Sciences' GILD -2.11% proposed single-tablet, fixed-dose combination treatment – due to be approved in late 2014/early 2015 – as an adequate justification for higher pricing versus less convenient therapies (i.e. more tablets) that deliverer a similar level of efficacy.
Continue reading...
Tuesday, December 10, 2013
AbbVie Demonstrates 96 percent SVR(12) Phase III Treatment-Experienced Patients with Geno 1 Hepatitis C
New In January 2014
New England Journal of Medicine Original Article
View Full Text @ NATAP
December 2013
AbbVie Demonstrates 96 percent SVR(12) in its Phase III Study of Treatment-Experienced Patients with Genotype 1 Hepatitis C
-Results further confirm phase II studies, with consistent virologic response and tolerability profile-
-SAPPHIRE-II is the second of six phase III trials studying the investigational 3D regimen-
-Future data anticipated from AbbVie's clinical trials examines 3D regimen with and without ribavirin, as well as treatment of hepatitis C in patients with cirrhosis-
"SAPPHIRE-II demonstrates that treatment-experienced genotype 1 HCV patients achieved high rates of virologic response with AbbVie's interferon-free, all-oral 3D regimen plus ribavirin," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Completion of the two placebo-controlled SAPPHIRE studies is an important step in AbbVie's HCV clinical development program. We look forward to the results of studies looking at AbbVie's 3D regimen with and without ribavirin in different patients, as well as data from our dedicated study in patients with cirrhosis."
About Study M13-098 (SAPPHIRE-II)
Following SAPPHIRE-I, SAPPHIRE-II is the second placebo-controlled trial and the second of six phase III trials supporting AbbVie's investigational 3D regimen for the treatment of GT1 hepatitis C patients. AbbVie will disclose detailed SAPPHIRE-II results at future scientific congresses and in publications.
SAPPHIRE-II is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with ABT-333 (250mg), ribavirin (weight-based), both dosed twice daily, and the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg) and dosed once daily in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and ribavirin.
The study population consisted of 394 GT1 treatment-experienced patients with no evidence of liver cirrhosis with 297 patients randomized to the 3D regimen plus ribavirin for 12 weeks, and 97 patients randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the 3D regimen plus ribavirin for 12 weeks. In the study, 49 percent of patients were prior null responders to pegylated interferon and ribavirin, generally considered among the most difficult to treat successfully.
Following 12 weeks of treatment with AbbVie's 3D regimen plus ribavirin, 96 percent (n=286/297) of patients achieved SVR12 based on intent-to-treat analysis where patients with missing values for any reason were considered treatment failures. The SVR12 rates in GT1a and GT1b patients were 96 percent (166/173) and 97 percent (119/123), respectively. One subject had HCV genotype 1 and achieved SVR12, but was unable to be subgenotyped.
The most commonly reported adverse events in both the 3D and placebo arms were headache, fatigue and nausea. Discontinuations due to adverse events were reported in three (1 percent) patients receiving the 3D regimen and no patients receiving placebo. Virologic relapse or breakthrough was noted in 2 percent of patients receiving the 3D regimen plus ribavirin.
Additional information about AbbVie's phase III studies can be found on www.clinicaltrials.gov.
AbbVie's HCV Development Program
The clinical program supporting our 3D regimen includes more than 2,300 GT1 patients in more than 25 countries around the world. The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral 3D regimen with or without ribavirin with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis. Results from the remaining four studies in AbbVie's phase III program will be available in the coming months, supporting regulatory submissions starting in the second quarter of 2014.
Overview of AbbVie's phase III clinical program is as follows:
a projected study population
b ABT-450/ritonavir
c ABT-267 is co-formulated with ABT-450/r, administered as two pills once daily
The 3D regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations. In May of 2013, AbbVie's investigational 3D regimen with and without ribavirin for HCV GT1 was designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA).
ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.
Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.
There are special safety considerations when prescribing these drugs in approved populations.
Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.
Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, automimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score ≥6.
See approved product labels for more information.
About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott. 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. In 2013, AbbVie employs approximately 21,000 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 2012 Annual Report on Form 10-K/A, 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.
[1] Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15.
[2] Comparison based on review of data from clinicaltrials.gov for phase 3a programs of Gilead, BMS and BI as of November 15, 2013
New England Journal of Medicine Original Article
View Full Text @ NATAP
Abstract @ NEJM
View Article @ HCV New Drugs
Phase 2b Trial of Interferon-free Therapy for Hepatitis C Virus Genotype 1
Phase 2b Trial of Interferon-free Therapy for Hepatitis C Virus Genotype 1
New England Journal Abstract-
The study evaluated an 8, 12, and 24-week all-oral, interferon-free treatment regimen among 571 patients with HCV genotype 1 who were previously untreated or who had failed prior therapy. The study, led by Kris V. Kowdley, MD, from the Virginia Mason Medical Center, Seattle, Washington, evaluated various dosage combinations of the NS3/4A protease inhibitor ABT-450 with ritonavir (ABT-450/r), combined with nonnucleoside NS5B polymerase inhibitor ABT-267, ABT-333, or both. All but 1 subgroup also received ribavirin.
The researchers found that SVR ranged from 83% to 100% across all treatment groups. The SVR at 24 weeks among previously untreated patients administered ABT-450/r plus ribavirin was 88% among those treated for 8 weeks and 95% among those treated for 12 weeks. Treatment beyond 12 weeks did not appear to confer any additional benefit.
(full text @ NATAP)
The study evaluated an 8, 12, and 24-week all-oral, interferon-free treatment regimen among 571 patients with HCV genotype 1 who were previously untreated or who had failed prior therapy. The study, led by Kris V. Kowdley, MD, from the Virginia Mason Medical Center, Seattle, Washington, evaluated various dosage combinations of the NS3/4A protease inhibitor ABT-450 with ritonavir (ABT-450/r), combined with nonnucleoside NS5B polymerase inhibitor ABT-267, ABT-333, or both. All but 1 subgroup also received ribavirin.
The researchers found that SVR ranged from 83% to 100% across all treatment groups. The SVR at 24 weeks among previously untreated patients administered ABT-450/r plus ribavirin was 88% among those treated for 8 weeks and 95% among those treated for 12 weeks. Treatment beyond 12 weeks did not appear to confer any additional benefit.
(full text @ NATAP)
December 2013
AbbVie Demonstrates 96 percent SVR(12) in its Phase III Study of Treatment-Experienced Patients with Genotype 1 Hepatitis C
-Results further confirm phase II studies, with consistent virologic response and tolerability profile-
-SAPPHIRE-II is the second of six phase III trials studying the investigational 3D regimen-
-Future data anticipated from AbbVie's clinical trials examines 3D regimen with and without ribavirin, as well as treatment of hepatitis C in patients with cirrhosis-
Dec 10, 2013
NORTH CHICAGO, Ill., Dec. 10, 2013 /PRNewswire/
-- AbbVie (NYSE: ABBV) released phase III results for the
investigational three direct-acting-antiviral (3D) regimen plus
ribavirin in patients with chronic, genotype 1 (GT1) hepatitis C virus
(HCV) infection. In the 394-patient SAPPHIRE-II study, 96 percent of
patients who previously failed pegylated interferon and ribavirin
treatment, including approximately 49 percent of who were prior null
responders, achieved sustained virologic response at 12 weeks (SVR12) with the regimen. The majority of patients were GT1a, considered a difficult-to-treat subtype, and the SVR12 rates of GT1a and GT1b were 96 percent and 97 percent, respectively.
Virologic relapse or breakthrough was noted in 2 percent of patients receiving the 3D regimen plus ribavirin. In addition, the discontinuation rate due to adverse events was 1 percent.
Globally, approximately 160 million people are chronically infected
with hepatitis C[1]. AbbVie's multinational HCV program is the largest
all-oral, interferon-free clinical program in GT1 patients being
conducted to date[2]. GT1 (with subtypes 1a and 1b) is the most
prevalent genotype worldwide, with a higher prevalence of 1a in the U.S.
and 1b in Europe.Virologic relapse or breakthrough was noted in 2 percent of patients receiving the 3D regimen plus ribavirin. In addition, the discontinuation rate due to adverse events was 1 percent.
"SAPPHIRE-II demonstrates that treatment-experienced genotype 1 HCV patients achieved high rates of virologic response with AbbVie's interferon-free, all-oral 3D regimen plus ribavirin," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "Completion of the two placebo-controlled SAPPHIRE studies is an important step in AbbVie's HCV clinical development program. We look forward to the results of studies looking at AbbVie's 3D regimen with and without ribavirin in different patients, as well as data from our dedicated study in patients with cirrhosis."
About Study M13-098 (SAPPHIRE-II)
Following SAPPHIRE-I, SAPPHIRE-II is the second placebo-controlled trial and the second of six phase III trials supporting AbbVie's investigational 3D regimen for the treatment of GT1 hepatitis C patients. AbbVie will disclose detailed SAPPHIRE-II results at future scientific congresses and in publications.
SAPPHIRE-II is a global, multi-center, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 12 weeks of treatment with ABT-333 (250mg), ribavirin (weight-based), both dosed twice daily, and the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg) and dosed once daily in non-cirrhotic, GT1a and GT1b HCV-infected, treatment-experienced adult patients who previously failed treatment with pegylated interferon and ribavirin.
The study population consisted of 394 GT1 treatment-experienced patients with no evidence of liver cirrhosis with 297 patients randomized to the 3D regimen plus ribavirin for 12 weeks, and 97 patients randomized to placebo for the initial 12 weeks. Patients initially randomized to placebo for the first 12 weeks then received open-label treatment with the 3D regimen plus ribavirin for 12 weeks. In the study, 49 percent of patients were prior null responders to pegylated interferon and ribavirin, generally considered among the most difficult to treat successfully.
Following 12 weeks of treatment with AbbVie's 3D regimen plus ribavirin, 96 percent (n=286/297) of patients achieved SVR12 based on intent-to-treat analysis where patients with missing values for any reason were considered treatment failures. The SVR12 rates in GT1a and GT1b patients were 96 percent (166/173) and 97 percent (119/123), respectively. One subject had HCV genotype 1 and achieved SVR12, but was unable to be subgenotyped.
The most commonly reported adverse events in both the 3D and placebo arms were headache, fatigue and nausea. Discontinuations due to adverse events were reported in three (1 percent) patients receiving the 3D regimen and no patients receiving placebo. Virologic relapse or breakthrough was noted in 2 percent of patients receiving the 3D regimen plus ribavirin.
Additional information about AbbVie's phase III studies can be found on www.clinicaltrials.gov.
AbbVie's HCV Development Program
The clinical program supporting our 3D regimen includes more than 2,300 GT1 patients in more than 25 countries around the world. The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating an interferon-free, all-oral 3D regimen with or without ribavirin with the goal of producing high SVR rates in as many patients as possible, including those that typically do not respond well to treatment, such as previous non-responders to interferon-based therapy or patients with advanced liver fibrosis or cirrhosis. Results from the remaining four studies in AbbVie's phase III program will be available in the coming months, supporting regulatory submissions starting in the second quarter of 2014.
Overview of AbbVie's phase III clinical program is as follows:
Study
|
Patients (N)
|
Treatment Regimen
|
Treatment Duration
|
SAPPHIRE-I
|
GT1, treatment-naive
(631)
|
|
12 weeks
|
|
12 weeks, then active treatment for 12 weeks
| ||
SAPPHIRE-II
|
GT1, treatment-experienced
(394)
|
|
12 weeks
|
|
12 weeks, then active treatment for 12 weeks
| ||
PEARL-II
|
GT1b, treatment-experienced
(210 a)
|
|
12 weeks
|
|
12 weeks
| ||
PEARL-III
|
GT1b, treatment-naive
(400 a)
|
|
12 weeks
|
|
12 weeks
| ||
PEARL-IV
|
GT1a, treatment-naive
(300 a)
|
|
12 weeks
|
|
12 weeks
| ||
TURQUOISE-II
|
GT1, treatment-naive and treatment-experienced (with compensated cirrhosis)
(380 a)
|
|
12 weeks
|
|
24 weeks
|
a projected study population
b ABT-450/ritonavir
c ABT-267 is co-formulated with ABT-450/r, administered as two pills once daily
The 3D regimen consists of boosted protease inhibitor ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase inhibitor ABT-333. The combination of three different mechanisms of action interrupts the HCV replication process with the goal of optimizing SVR rates across different patient populations. In May of 2013, AbbVie's investigational 3D regimen with and without ribavirin for HCV GT1 was designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA).
ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV.
Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.
There are special safety considerations when prescribing these drugs in approved populations.
Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.
Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, automimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score ≥6.
See approved product labels for more information.
About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott. 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. In 2013, AbbVie employs approximately 21,000 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 2012 Annual Report on Form 10-K/A, 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.
[1] Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15.
[2] Comparison based on review of data from clinicaltrials.gov for phase 3a programs of Gilead, BMS and BI as of November 15, 2013
SOURCE AbbVie Inc.
For
further information: Media: Elizabeth Hoff, +1 (847) 935-4236,
elizabeth.hoff@abbvie.com, or Javier Boix, +1 (847) 937-6113,
javier.boix@abbvie.com, or For Investor Relations: Elizabeth Shea, +1
(847) 935-2211, elizabeth.shea@abbvie.com
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