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FDA Advisory Committee Gives Positive Opinions on HCV Drugs Simeprevir and Sofosbuvir


The Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) this week gave unanimous recommendations for approval of 2 next-generation direct-acting antivirals for hepatitis C, Janssen's simeprevir (formerly TMC435) and Gilead Science's sofosbuvir (formerly GS-7977 and PSI-7977).

The advent of direct-acting antivirals (DAAs) has brought about a revolution in the treatment of chronic hepatitis C. The first such drugs -- the HCV protease inhibitors boceprevir (Victrelis) and telaprevir (Incivek) -- used with pegylated interferon and ribavirin can dramatically shorten treatment duration and raise sustained virological response rates, but they also come with added side effects.

Several next-generation DAAs in the pipeline are more effective, more convenient (many once-daily), and better tolerated. While the earliest such drugs will still be used as add-ons to interferon-based therapy, all-oral, interferon-free regimens are expected to become available within the next couple years.

On October 24 the FDA committee voted unanimously to recommend approval of simeprevir, an HCV NS3/4A protease inhibitor, which has shown promising results both in combination with pegylated interferon/ribavirin and in several interferon-free regimens. It was approved at a dose of 150 mg once-daily for use by genotype 1 hepatitis C patients, either treatment-naive or prior non-responders, with compensated liver disease including cirrhosis.

Approval for simeprevir was supported in part by data from the pivotal Phase 3 QUEST-1 and QUEST-2 trials in treatment-naive patients and PROMISE in patients who relapsed after prior interferon-based therapy, as well as data from the Phase 2b ASPIRE study in prior non-responders. Simeprevir is less effective among people with subtype 1a HCV carrying the Q80K mutation. Side effects may include rash and photosensitivity (increased susceptibility to sunburn). Simeprevir briefing materials used by the committee are available online.

On October 25 the committee again voted unanimously in favor of approving sofosbuvir, the first nucleotide analog HCV polymerase inhibitor. The recommendation covers both use with interferon-based therapy for treatment-naive people with HCV genotypes 1 or 4 and use in dual therapy with ribavirin for people with easier-to-treat HCV genotypes 2 or 3, making it the first approved interferon-free regimen.

Sofosbuvir has likewise shown good efficacy both in combination with pegylated interferon/ribavirin and in all-oral regimens. These include sofosbuvir/ribavirin dual therapy for people with genotypes 2/3 and combinations with the HCV NS5A inhibitors daclatasvir (formerly BMS-700952) or ledipasvir (GS-5885) for patients with HCV genotype 1. Sofosbuvir briefing materials are also available online.

The FDA committee considered approval of simeprevir for use only in interferon-based therapy, and sofosbuvir as both an interferon add-on and for use in an interferon-free regimen for people with HCV genotype 2/3. Neither was considered for use in interferon-free regimens for people with HCV genotype 1. The two drugs have been tested together and demonstrated good efficacy in early studies, but this would not yet be an approved indication.

Final decisions about approval of simeprevir and sofosbuvir are expected by the end of 2013. The full FDA is not required to follow its advisory committees' recommendations, but it usually does so.



Janssen Research and Development. FDA Advisory Committee Recommends Approval of Simeprevir for Combination Treatment of Genotype 1 Chronic Hepatitis C in Adult Patients. Press release. October 24, 2013.

Gilead Sciences. FDA Advisory Committee Supports Approval of Gilead’s Sofosbuvir for Chronic Hepatitis C Infection. Press release. October 25, 2013.

T Clarke. FDA panel backs Gilead's hepatitis C drug sofosbuvir. Reuters. October 25, 2013.

Briefing Information for the October 25, 2013 Meeting of the Antiviral Drugs Advisory Committee (sofosbuvir).

Briefing Information for the October 24, 2013 Meeting of the Antiviral Drugs Advisory Committee (simeprevir).