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Simeprevir, a hepatitis C virus protease inhibitor, has been approved as a treatment for chronic hepatitis C in patients who have compensated liver disease, including cirrhosis, the Food and Drug Administration announced.
For patients with HCV genotype 1 infections, simeprevir’s approved dose is a 150-mg capsule taken once a day with food, in combination with peginterferon-alfa and ribavirin for 24-48 weeks. Before treatment, clinicians should screen patients with genotype 1a HCV infections for the presence of the NS3 Q80K polymorphism, which was associated with lower response rates in studies, "and to consider alternative therapy if the strain is detected," according to the FDA’s Nov. 22 statement announcing the approval.
Simeprevir is the third protease inhibitor to be approved by the FDA for treatment of hepatitis C. Boceprevir (Victrelis) and telaprevir (Incivek) were approved in 2011 and have been the standard of care, but they require taking 6-12 pills a day. Simeprevir is an NS3/4A protease inhibitor, which blocks the viral protease enzyme that enables HCV to replicate in host cells, according to Janssen Pharmaceuticals, which will market the drug as Olysio.
Simeprevir’s simpler dosing regimen, effectiveness, and favorable risk-benefit profile in clinical trials were cited by the FDA’s antiviral drug advisory committee in its unanimous recommendation to approve the drug at a meeting on Oct. 24.
Approval is based on five trials of 2,026 treatment-naive and treatment-experienced patients with chronic hepatitis C who were randomized to simeprevir plus peginterferon-alfa and ribavirin (PR) or to placebo plus PR. The primary endpoint was sustained virologic response rate at 12 weeks after treatment was planned to end (SVR12). SVR was defined as an HCV RNA level that was undetectable or detected only below a prespecified value.
Among the treatment-naive patients, the SVR12 rate was 80% for those treated with simeprevir plus PR and 50% in those who received placebo plus PR. In a study of treatment-experienced patients, 79% of those treated with the simeprevir regimen and 37% of those on peginterferon-alfa and ribavirin achieved SVR12.
In another study of treatment-experienced patients that included prior relapsers, partial responders, and null responders (those who did not respond to previous treatments at all), the addition of simeprevir to PR improved response rates when compared with treatment with PR alone, according to the FDA.
Rash, pruritus, and nausea were the most common adverse effects associated with treatment in the studies, the FDA said. There were cases of serious photosensitivity that required hospitalization, and the prescribing information recommends that patients use sun protection and limit sun exposure during treatment. The prescribing information notes that dosing recommendations cannot be made at this time for patients with moderate to severe hepatic impairment or those of East Asian descent. At the FDA panel meeting, company officials said that the appropriate dose in this population was being investigated.
Simeprevir was approved for treatment of genotype 1 HCV infection in September 2013 in Japan, where it is marketed as Sovriad (at a lower 100-mg dose), and in November in Canada, where it is marketed as Galexos, according to Janssen. Simeprevir is under review in Europe for the treatment of genotype 1 or 4 HCV.
Imminent approval of sofosbuvir, another HCV treatment with a different mechanism of action, is expected.