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FDA Approves Simeprevir (Olysio) for Chronic Hepatitis C


The U.S. Food and Drug Administration last Friday approved Janssen/Medivir's next-generation hepatitis C virus (HCV) protease inhibitor simeprevir -- to be marketed under the brand name Olysio -- as an add-on to interferon-based therapy for the treatment of people with genotype 1 chronic hepatitis C. It is not yet approved for use in interferon-free combinations.

The advent of direct-acting antivirals (DAAs) has brought about a revolution in the treatment of chronic hepatitis C. The first such agents have been approved for use with pegylated interferon and ribavirin, shortening treatment duration and dramatically increasing cure rates.

Approval was based on data from 5 randomized clinical trials enrolling more than 2000 patients. Simeprevir (formerly TMC435), an HCV NS3/4A protease inhibitor, has shown good efficacy both in combination with pegylated interferon/ribavirin and in several interferon-free regimens. However, last week's approval does not include interferon-free use.

The FDA approved simeprevir for use at a dose of 150 mg once-daily in combination with pegylated interferon alfa-2a (Pegasys) or alfa-2b (PegIntron) and weight-based ribavirin. Triple therapy is used for 12 weeks, with pegylated interferon/ribavirin alone continued for an additional 12 weeks for treatment-naive patents and prior relapsers, or 36 more weeks for prior partial and null responders.

Simeprevir has no food requirements. It is mainly metabolized by the CYP3A4 enzyme in the liver, but does not affect CYP3A4 activity. Co-administration with certain other medications may lead to drug-drug-interactions that raise or lower levels of simeprevir or the other drugs, as described in the prescribing information.

Simeprevir was approved for people with compensated liver disease including cirrhosis. It is effective for treatment-naive patients -- with an overall efficacy of 80% -- and for prior interferon/ribavirin non-responders, but has not yet been tested in non-responders to triple therapy including the first-generation HCV protease inhibitors, boceprevir (Victrelis) or telaprevir (Incivek).

Simeprevir is active against HCV subtypes 1a and 1b, but it does not work as well for people with 1a and a pre-existing Q80K polymorphism. The FDA strongly recommends screening for this genetic variant prior to treatment and consideration of alternative therapy if present.

Simeprevir is generally safe and well-tolerated but it may cause side effects including rash, pruritis (itching), and photosensitivity (increased susceptibility to sunburn); people taking the drug are advised to use sunscreen and wear protective clothing. Interferon and ribavirin are also associated with several side adverse events such as depression and anemia.

"Given the complexity of the condition, Olysio was studied in a number of different patient populations, including individuals who have relapsed or failed to respond to previous treatments," clinical trial investigator Douglas Dieterich from Mount Sinai School of Medicine said in a Janssen press release. "The FDA approval of Olysio is an important milestone for people living with chronic hepatitis C as it means that patients have a new treatment option with the potential to cure this challenging disease."

Over years or decades chronic hepatitis C infection can lead to serious liver disease including advanced fibrosis, cirrhosis (scarring), and hepatocellular carcinoma. Studies have shown that effective treatment can reduce or halt disease progression, though people who already have cirrhosis may still develop liver cancer and should continue to be screened.

Full prescribing information for Olysio is available online.



Food and Drug Administration. FDA Approves New Treatment for Hepatitis C Virus. Press release. November 22, 2013.

R Klein and K Struble. FDA Hepatitis Update -- Olysio (simeprevir) for the treatment of chronic hepatitis C in combination antiviral treatment. November 25, 2013.


Janssen Therapeutics. OLYSIO (simeprevir) Receives FDA Approval for Combination Treatment of Chronic Hepatitis C. Press release. November 22, 2013.

Medivir. Simeprevir has been approved in the USA as a new treatment for hepatitis C. Press release. November 22, 2013.