Rounding the turn in the final drive to a likely FDA approval, an NIH-sponsored study of Gilead's sofosbuvir combined with ribavirin demonstrated that the experimental therapy provided a "safe and effective" interferon-free approach for even some of the toughest hepatitis C cases.
For this Phase II study, NIH investigators recruited 60 patients with genotype-1 HCV, including 50 African-Americans, who are disproportionately affected by the disease and often found in the groups of patients most difficult to treat. The group included 10 patients with mild to moderate liver fibrosis. All 9 who completed a 12-week course had an undetectable level of the virus and were deemed cured at 24 weeks.
In the second group of 50 patients, 13 suffered from serious liver damage--another likely indicator of being treatment-resistant. Twenty-five members of the group received doses of ribavirin based on weight, with the other 25 getting a low dose and all taking sofosbuvir. Twenty-four members of the weight-based group had undetectable levels of the hepatitis C virus at 12 weeks and 17 were considered cured at 24 weeks. In the low-dose group, three dropped out and only 12 were considered cured at 24 weeks.
"We saw an overall cure rate of about 70% using regimens that did not include interferon," said Dr. Shyam Kottilil, the principal investigator. "This is an encouraging result, especially considering the proportion of volunteers who had characteristics--such as being male, having HCV genotype-1 infection, being African-American and having advanced liver damage--that are recognized as predictors of poor response to treatment."
There are caveats. Sofosbuvir is being tested in cocktails that will be far more effective--in particular as a combination therapy with Gilead's ledipasvir, which was designated as a breakthrough therapy at the FDA. AbbVie ($ABBV; ABT-450/r + ABT-267 + ABT-333), Bristol-Myers Squibb ($BMY), Vertex ($VRTX) and others are racing along with their own programs which will help overturn a market for therapies still dependent on interferon-based formulations. But the data helps secure Gilead's ($GILD) lead position in the race to develop the first interferon-free regimen for hepatitis C, which afflicts millions of Americans.
The FDA has a December deadline to decide on Gilead's NDA for sofosbuvir. Peak sales estimates for sofosbuvir are ranked in the billions--Barclays pegged it at $3.8 billion--making this one of the most promising drugs in development today.
NIAID Director and study co-author Dr. Anthony S. Fauci also endorsed the drug.
"There is a pressing need for hepatitis C virus treatments that are less burdensome to the patient, have fewer side effects and take less time to complete. Building on previous work, this trial provides compelling evidence that interferon-free regimens can be safe and effective," said Fauci.
The data were published in JAMA.
- here's the release from the NIH
- and the JAMA abstract