Gilead Sciences, Inc. (Nasdaq: GILD) today announced that detailed results from four Phase 3 clinical trials (NEUTRINO, FISSION, POSITRON and FUSION) evaluating sofosbuvir, the company's investigational once-daily nucleotide NS5B inhibitor for the treatment of chronic hepatitis C virus (HCV) infection, will be presented this week in oral sessions at the 48th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2013) in Amsterdam, The Netherlands. In addition, detailed results from the four clinical studies have also been published online in two papers, ahead of print, in The New England Journal of Medicine (NEJM).
“There remains an urgent unmet medical need for individuals diagnosed with chronic hepatitis C infection”
In the four trials, sofosbuvir was administered to nearly 1,000 patients with chronic HCV infection as part of an all-oral 12-week or 16-week treatment regimen in combination with ribavirin (RBV) in genotypes 2 and 3, or with RBV and pegylated interferon (peg-IFN) for 12 weeks in genotypes 1, 4, 5 and 6. Overall SVR12 rates (sustained viral response 12 weeks after completing therapy) from 50 to 90 percent were observed. Patients who achieve SVR12 are considered cured of their HCV infection.
A description of the four Phase 3 studies and SVR12 results are summarized in the table below. Detailed results from the Phase 3 studies of sofosbuvir are available at www.nejm.org/online-first.
"There remains an urgent unmet medical need for individuals diagnosed with chronic hepatitis C infection," commented Ira Jacobson, MD, Chief of the Division of Gastroenterology and Hepatology, Vincent Astor Distinguished Professor of Medicine, The Joan Sanford I. Weill Medical College of Cornell University, Attending Physician, New York-Presbyterian Hospital Cornell Campus. "The breadth of data from the Phase 3 program evaluating sofosbuvir will help physicians understand how to treat the disease in the future across various HCV genotypes and patient populations."
"In these particular studies, sofosbuvir-based HCV therapy demonstrated high efficacy rates and a favorable safety profile while reducing the need for interferon injections to 12 weeks, or eliminating interferon completely from the regimen," said Eric Lawitz, MD, President and Medical Director, The Texas Liver Institute, University of Texas Health Science Center, San Antonio. "Based on these findings, sofosbuvir, once approved, has the potential to play an important role in addressing the global hepatitis C epidemic."
The NS5b region of the HCV viral genome for all patients who relapsed was sequenced and no S282T mutations were observed by population or deep sequencing (1 percent cutoff). There was no change in susceptibility to sofosbuvir or RBV observed by phenotypic analyses.
With the exception of one patient in FISSION who was non-compliant, relapse accounted for all virologic failures. Adverse events were generally mild and included fatigue, nausea, headache, insomnia, pruritis, anemia and dizziness. Less than 2 percent of patients in the sofosbuvir treatment groups discontinued due to adverse events.
On April 8, Gilead submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for sofosbuvir for the treatment of HCV infection. The data submitted in the NDA support the use of sofosbuvir and RBV as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and peg-IFN for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.
Gilead plans to file for regulatory approval of sofosbuvir in other geographies, including the European Union, in the second quarter of 2013. The European Medicines Agency (EMA) has accepted Gilead's request for accelerated assessment for sofosbuvir, a designation that is granted to new medicines of major public health interest. Accelerated assessment could shorten the EMA's review time of sofosbuvir by two months. Granting of accelerated assessment does not guarantee a positive opinion from the CHMP or approval by the European Commission.
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