9 APRIL 2013
Gilead Sciences today announced that the company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for approval of sofosbuvir, a once-daily oral nucleotide analogue for the treatment of chronic hepatitis C virus (HCV) infection. The data submitted in this NDA support the use of sofosbuvir and ribavirin (RBV) as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and pegylated interferon (peg-IFN) for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.
Chronic HCV infection affects up to four million Americans, particularly individuals born between 1946 and 1964. The disease is the leading cause of liver cancer and liver transplantation in the United States. Treatment for HCV currently includes 24-48 weeks of therapy with peg-IFN, which has to be injected and is associated with significant side effects, leaving some patients unable to complete therapy. If approved, sofosbuvir would shorten HCV therapy to 12 to 16 weeks, and depending on the genotype, would either eliminate or reduce the duration of peg-IFN injections.
“Current therapies are not suitable for large numbers of patients with HCV infection, and are challenging to take and tolerate,” said John C. Martin, PhD, Chairman and Chief Executive Officer of Gilead Sciences. “Sofosbuvir’s antiviral potency, safety profile and once-daily administration have the potential to improve cure rates by simplifying and shortening therapy for patients with this disease.”
The sofosbuvir NDA is supported primarily by data from four phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION, in which 12 or 16 weeks of sofosbuvir-based therapy was found to be superior or non-inferior to currently available treatment options or historical controls, based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12). Patients who achieve SVR12 are considered cured of HCV.
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.
Sofosbuvir (formerly PSI-7977 or GS-7977) is an experimental drug candidate for the treatment of hepatitis C. It was discovered at Pharmasset and then acquired for development by Gilead Sciences. It is currently in Phase III clinical trials.
Sofosbuvir is a prodrug that is metabolized to the active antiviral agent 2′-deoxy-2′-α-fluoro-β-C-methyluridine-5′-monophosphate.
Sofosbuvir is a nucleotide analogue inhibitor of the hepatitis C virus (HCV) polymerase. The HCV polymerase or NS5B protein is a RNA-dependent RNA polymerase critical for the viral cycle.
Sofosbuvir is being studied in combination with pegylated interferon and ribavirin, with ribavirin alone, and with other direct-acting antiviral agents. It has shown excellent clinical efficacy when used either with pegylated interferon/ribavirin or in interferon-free combinations. In particular, combinations of sofosbuvir with NS5A inhibitors, such as daclatasvir or GS-5885, have shown sustained virological response rates of up to 100% in people infected with HCV.
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