HCV Standard of Care Controversy: report from FDA Hearing; what can new era of HCV antivirals offer by Ira Jacobson; Key Treatment Outcomes for Boceprevir & Telaprevir, Essentially Doubling SVR Rates
Reported by Jules Levin
A very important discussion occurred at the very end of the FDA meeting yesterday, that is what is the new "standard of care (SOC)" for HCV. Clearly after the 2 new HCV protease inhibitors are approved, probably within a month, boceprevir or telaprevir in combinatin with peginterferon+ribavirin become the new SOC. Does this make peg/rbv no longer the standard of care, FDA officials asked the committee to comment on. I say YES, it now becomes unethical to use Peg/rbv in new studies. Well, this affects the 2 phase 3 studies started recently by Tibotec for their new HCV protease inhibitor TMC435 and for
Boerhinger Ingelheim's new HCV protease inhibitor BI201335, which was announced yesterday that they started enrolling for their phase 3 study. In both studies peg/rbv is the comparator arm treatment. In addition for future planned studies what should the comparator study arm be: peg/ifn or one of the 2 new protease inhibitors plus peg/rbv. I say the latter. In addition this creates a conundrum for HCV/HIV coinfection because we have yet to characterize understand the outcome of treatment for coinfection with the 2 new HCV protease inhibitors in coinfected patients although recently preliminary data in a small group of coinfected patients receiving telaprevir+peg/rbv was presented at a conference yet the boceprevir coinfection study remains ongoing with no data yet reported. The drug-drug interactions between HIV ARTs and the 2 new HCV protease inhibitors are a concern and there are many unanswered questions about these interactions and how to use them together with the 2 new HCV drugs. In the coinfection telaprevir study patients were taking Reyataz/r or efavirenz and in preliminry analysis the early outcomes were pretty similar to that seen in HIV-uninfected but we have yet to see SVR data, the study was small, and there were serious interactions reported with some other key HIV ARTs. The other important issue NOT discussed yesterday is what should be the comparator arm SOC in future studies of new drugs in treatment-experienced patients. So why is this important. If you are for example studying the 2 new Pharmasset nucleotides in treatment-experienced patients, is using one of the new HCV PIs+peg/rbv acceptable considering this may perform less well, patients may not want to enroll in the study since they can get the new drugs through their clinicians and perhaps such a study is now not ethical...Continue reading...
Hepatitis C drug called a ‘miraculous advance’
SILVER SPRING, Md. — A new treatment for hepatitis C could soon be on the market if the Food and Drug Administration takes the advice of an advisory committee.
The committee unanimously approved the first of two new drugs to treat chronic hepatitis C genotype 1 infection. Hepatitis C is a chronic viral disease that causes inflammation and swelling of the liver.The drug, boceprevir, is a new class of protease inhibitor manufactured by pharmaceutical giant Merck & Co., and would be used in combination with ribavirin and peginterferon — the current standard of care. Boceprevir prevents the virus from replicating, and studies show the three-drug cocktail is more effective than the two-drug regimen
A big week for treatment of Hepatitis C Virus: 2 new drugs get FDA panel OK
There is an enormous amount of excitement in the medical community and in patients with Hepatitis C virus infections. An estimated 170 million people have chronic hepatitis C virus (HCV) infection, and in many of those people liver cirrhosis and eventual liver transplantation is the only option. Current treatment for patients is injection of interferon alfa and oral ribaviron for up to 12 months, and only 40-50% of treated patients respond positively to the treatment. In the other 50-60% of patients who do not respond, the only path is retreatment with the same course of drugs, and chance of success the second time around is minimal. Both Merck and Vertex have been developing oral HCV inhibitors Both companies have tested these drugs in combination with interferon and ribaviron, and have demonstrated a tremendous increase in treatment success with this triple course of therapy. Both companies were asked to present their data to a FDA panel of experts this week in preparation for a decision by the FDA for drug approval expected next month
New Drugs For Hepatitis C: Part 1 – Boceprevir And Telaprevir Provide Higher Cure Rates
This article is first in a two-part series that will discuss the benefits and drawbacks of two drugs, boceprevir and telaprevir, which are being developed for hepatitis C. Part 1 discusses the efficacy of the two drugs in clinical trials. Part 2 will discuss the complications and side effects for each drug.
A United States Food and Drug Administration advisory committee unanimously recommended this week that two new hepatitis C drugs, boceprevir and telaprevir, be approved. If the FDA follows the committee’s recommendations, people with hepatitis C – including those who are co-infected with HIV – will have promising new treatment choices. However, these new treatment options also have new side effects and potentially complicated dosing regimens.
In natural history studies of hepatitis C virus (HCV) infection, women have a lower risk of disease progression to cirrhosis. Whether gender influences outcomes of HCV in the post-transplant setting is unknown. All patients transplanted for HCV-related liver disease from 2002-2007 at 5 U.S. transplant centers were included. The primary outcome was development of advanced disease, defined as biopsy-proven bridging fibrosis or cirrhosis. Secondary outcomes included death, graft loss, and graft loss with advanced recurrent disease. 1,264 patients were followed for a median of 3.0 years (IQR 1.8-4.7) – 304 (24%) were female. The cumulative rate of advanced disease at 3-years was 38% for females and 33% for males (p=0.31) but after adjustment for recipient age, donor age, donor anti-HCV positivity, post-transplant HCV treatment, cytomegalovirus infection and center, female gender was an independent predictor of advanced recurrent disease (HR, 1.31; 95%CI, 1.02-1.70; p=0.04). Among women, older donor age and treated acute rejection were the primary predictors of advanced disease. The unadjusted cumulative 3–year rates of patient and graft survival were numerically lower in females than males, 75% vs. 80% and 74% vs. 78%, and in multivariable analyses, female gender was an independent predictor for death (HR, 1.30; 95%CI, 1.01-1.67; p=0.04) and graft loss (HR, 1.31; 95%CI, 1.02-1.67; p=0.03).
Female gender represents an under-recognized risk factor for advanced recurrent HCV disease and graft loss. Further studies are needed to determine whether modification of donor factors, immunosuppression, and post-transplant therapeutics can equalize HCV-specific outcomes in women and men. (HEPATOLOGY 2011.)
Chronic Hepatitis C Treatment, Pegasys®, Designated For Priority Reviewby Ministry Of Health, Labour And Welfare For The Indication Of Hepatitis B
30 April 2011
Chugai Pharmaceutical Co., Ltd. (hereafter ''Chugai'') [Head Office: Chuo-ku, Tokyo. President: Osamu Nagayama] announced today that on April 11, the Japanese Ministry of Health, Labour and Welfare designated Pegasys®...
US Appeals Court opens federal funding for stem cell research
The US Federal Court of Appeals has overturned an August 2010 ban on federal funding of embryonic stem cell research, paving the way for broader exploration of how stem cells function and how they can be harnessed to treat a wide range of currently incurable diseases.