FDA staff stated in documents released Wednesday ahead of an FDA advisory panel meeting on October 25 that Gilead Sciences' experimental drug sofosbuvir has "a favourable benefit-risk assessment...as part of a combination regimen for the treatment of chronic hepatitis C." Agency reviewers noted that for some patients, the oral nucleotide polymerase inhibitor "provides the first all-oral, interferon-free treatment, as well as a shorter treatment duration and improved safety profile, compared to the current standard-of-care, interferon-based regimen."
Gilead said that in clinical testing, 90 percent of treatment-naïve patients infected with hepatitis C (HCV) genotypes 1, 4, 5 or 6 were cured after 12 weeks of treatment with sofosbuvir in combination with pegylated interferon and ribavirin, but agency reviewers noted that dosing for those with genotypes 5 or 6 could not be clarified as only seven of these patients had been studied. Nonetheless, they remarked that the "shorter 12-week [treatment] duration translates into a better tolerated side-effect profile," adding that "no major safety issues associated with sofosbuvir have been identified to date." The FDA mentioned that the drug was less effective in treatment-naïve patients infected with less common genotypes, curing about 67 percent of those patients.
Earlier this week, an FDA staff review of Johnson & Johnson and Medivir's oral protease inhibitor simeprevir found that the drug was effective in most patients infected with HCV, although they mentioned that patients should first be screened for the Q80K polymorphism, which reduces the drug's activity. At that time, Wells Fargo analyst Brian Abrahams suggested the FDA report confirms "sofosbuvir-based regimens will be the market leaders in 2014 and beyond," as no requirement for polymorphism testing is anticipated for Gilead's therapy. John McHutchison, Gilead's senior vice president of liver disease therapeutics, said "sofosbuvir seems to be the future of many of these highly effective all-oral regimens."
Gilead is looking to market sofosbuvir in combination with ribavirin in genotype 2- or 3-infected patients, as well as for those awaiting a liver transplant. Further, it is seeking approval of once-daily sofosbuvir combined with pegylated interferon and ribavirin for genotype 1-infected patients irrespective of previous treatment, as well as for treatment-naïve patients infected with HCV genotypes 4, 5 or 6. The company is also investigating sofosbuvir in combination with its experimental hepatitis C treatment ledipasvir with the goal of launching the all-oral combination about a year after sofosbuvir reaches the market. Meanwhile, data from a mid-stage study testing the combination of sofosbuvir with simeprevir, with or without ribavirin, is expected to be presented in early November at the American Association for the Study of Liver Diseases annual meeting.
The FDA is scheduled to decide whether to clear sofosbuvir by December 8, and McHutchison remarked that "this [would be] the first approval" of a "two- or three-stage programme." Citi analyst Yaron Weber said the FDA's review was "overall favourable and may potentially lead to a broad label" for Gilead's therapy, which he estimates could reach annual sales of $2.7 billion.
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