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Janssen Seeks Approval of Simeprevir + Sofosbuvir for HCV Genotype 1

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Janssen Research & Development has submitted a supplemental New Drug Application to the U.S. Food and Drug Administration (FDA) requesting approval of its HCV protease inhibitor simeprevir (Olysio) for use with Gilead Sciences' HCV polymerase inhibitor sofosbuvir (Sovaldi) for certain treatment-naive and previously treated genotype 1 hepatitis C patients.

The Phase 2 COSMOS trial showed that the drugs work well together without interferon or ribavirin, curing more than 90% of genotype 1 patients with or without cirrhosis.

Although the current indications in the product labels for the 2 drugs do not include their use in a dual combination with each other, recent guidelines from the American Association for the Study of Liver Diseases and Infectious Diseases Society of America and the European Association for the Study of the Liver recommend this regimen for some patients, especially those who are intolerant of or otherwise ineligible to receive interferon.

Cost is likely to be a barrier to using simeprevir and sofosbuvir together, given their respective prices of approximately $66,000 and $84,000 for a 12-week course. However, a recent study published in theMarch 28 advance edition of Hepatology found that simeprevir plus sofosbuvir taken for 12 weeks is cost-effective compared with sofosbuvir plus ribavirin taken for 24 weeks for interferon-intolerant or ineligible patients. The former regimen costs approximately $150,000 with sustained virological response rates ranging from 89% to 100%, while the latter regimen costs approximately $169,000 with SVR rates of 52% to 84%.

Below is an edited excerpt from a Janssen press release describing the recent FDA submission.

Janssen Submits Supplemental New Drug Application to U.S. FDA for Olysio (Simeprevir)for Once-Daily Use in Combination with Sofosbuvir for 12 Weeks for the Treatment of Adult Patients with Genotype 1 Chronic Hepatitis C

Filing Includes Data from Treatment-Naive Patients with Advanced Fibrosis and Null Responders with All Stages of Liver Fibrosis

Raritan, New Jersey -- May 7, 2014 -- Janssen Research & Development, LLC (Janssen) today announced it has submitted a Supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for simeprevir, an NS3/4A protease inhibitor marketed as OLYSIO in the United States, in combination with the nucleotide analog NS5B polymerase inhibitor sofosbuvir developed by Gilead Sciences, Inc. This regulatory submission is for the treatment of genotype 1 chronic hepatitis C (HCV) in adult treatment-naive patients with advanced fibrosis and null responders with all stages of liver fibrosis.

OLYSIO is currently approved for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen. OLYSIO efficacy has been established in combination with peginterferon alfa and ribavirin in HCV genotype 1-infected patients with compensated liver disease, including cirrhosis.

"Hepatitis C places a significant burden on the lives of those infected and if left untreated may cause significant damage to the liver, including cirrhosis and complications such as liver failure," said Gaston Picchio, Hepatitis Disease Area Leader, Janssen Research & Development. "This filing brings us closer to potentially offering these patients a once-daily all-oral treatment combination that includes the direct-acting antiviral agents simeprevir and sofosbuvir."

The regulatory submission for OLYSIO and sofosbuvir is supported by data from the Phase 2 COSMOS study which included treatment-naive patients with advanced fibrosis (METAVIR F3 to F4 scores) and null-responder patients with all stages of liver fibrosis (METAVIR F0 to F4 scores).

In April 2014, Janssen announced initiation of the Phase 3 OPTIMIST trials examining the safety and efficacy of simeprevir and sofosbuvir without interferon or ribavirin for the treatment of chronic genotype 1 HCV infection. In the first trial, known as OPTIMIST-1, the combination will be administered once daily for 8 or 12 weeks in chronic HCV genotype 1 infected patients without cirrhosis who are HCV treatment naive or treatment experienced. In the second trial, known as OPTIMIST-2, the combination will be administered once daily for 12 weeks in HCV genotype 1 infected patients with cirrhosis who are HCV treatment naive or treatment experienced. For more information please visit www.clinicaltrials.gov.

About OLYSIO (simeprevir)

OLYSIO is an NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB and indicated for the treatment of chronic hepatitis C infection in combination with pegylated interferon and ribavirin in HCV genotype 1 infected patients with compensated liver disease, including cirrhosis.

Janssen is responsible for the global clinical development of simeprevir and has exclusive, worldwide marketing rights, except in the Nordic countries. Medivir AB retains marketing rights for simeprevir in these countries under the marketing authorization held by Janssen-Cilag International NV. Simeprevir was approved for the treatment of chronic hepatitis C infection as part of an antiviral treatment regimen in combination with pegylated interferon and ribavirin in genotype 1 infected adults with compensated liver disease, including cirrhosis in September 2013 in Japan, in November 2013 in Canada and the U.S., and in March 2014 in Russia. A Marketing Authorization Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C and the Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending Marketing Authorization in the European Union for the use of simeprevir in combination with other medicinal products for the treatment of chronic HCV. This application is under review by the EMA.

5/12/14

Sources

Janssen Research & Development. Janssen Submits Supplemental New Drug Application to U.S. FDA for OLYSIO (Simeprevir) for Once-Daily Use in Combination with Sofosbuvir for 12 Weeks for the Treatment of Adult Patients with Genotype 1 Chronic Hepatitis C. Press release. May 7, 2014.

LM Hagan, MS Sulkowski, RF Schinazi, et al. Cost Analysis of Sofosbuvir/Ribavirin versus Sofosbuvir/Simeprevir for Genotype 1 HCV in Interferon Ineligible/Intolerant Individuals. Hepatology. March 28, 2014 (Epub ahead of print).