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Janssen Seeks to Update Label for All-Oral, Once-Daily Simeprevir (Olysio) With Phase III Data

Filing supported by findings from OPTIMIST-1 and OPTIMIST-2 trials

Janssen Therapeutics has announced the submission of a supplemental new drug application (sNDA) to the FDA to update the label for once-daily, all-oral simeprevir (Olysio).

 Simeprevir is a hepatitis C virus NS3/4A protease inhibitor approved for use with sofosbuvir (Sovaldi, Gilead Sciences) in adults with genotype-1 chronic hepatitis C (CHC) infection as a 12-week treatment for patients without cirrhosis or as a 24-week treatment regimen for patients with cirrhosis. Sofosbuvir is a nucleotide analog NS5B polymerase inhibitor.

Simeprevir was approved in November 2014 in combination with sofosbuvir based on data from a phase II study (COSMOS). The new sNDA is based on results from the phase III OPTIMIST-1 and OPTIMIST-2 trials, which evaluated 12 and 8 weeks of therapy for treatment-naïve and treatment-experienced adults with genotype-1 CHC infection without cirrhosis, and 12 weeks of therapy for treatment-naïve and treatment-experienced genotype-1 CHC adults with cirrhosis.

Results from the OPTIMIST trials were presented in April 2015 at the International Liver Congress 2015 of the European Association for the Study of the Liver (EASL) in Vienna, Austria.

The randomized, open-label OPTIMIST-1 trial investigated the efficacy and safety of the all-oral regimen of simeprevir and sofosbuvir (SMV/SOF) in treatment-naive and treatment-experienced genotype-1 CHC patients without cirrhosis. The study’s primary endpoint was the sustained virologic response at 12 weeks after treatment (SVR12) following 12 and 8 weeks of therapy with SMV/SOF compared with a historical control (i.e., patients previously treated with approved regimens containing a direct-acting antiviral, pegylated interferon, and ribavirin).

Ninety-seven percent (n = 150/155) of patients treated with SMV/SOF for 12 weeks achieved SVR12, which was superior to the SVR12 rate of 87% percent among the control subjects. SVR12 rates of 100% were observed among patients with the IL28B CC genotype (n = 43/43) and among those with baseline NS5A and NS3 Q80K polymorphisms (n = 9/9).

Patients treated with 8 weeks of SMV/SOF achieved an SVR12 rate of 83% (n = 128/155), which was not superior to the SVR12 rate of 83% in control subjects. High SVR12 rates were observed among patients with baseline HCV RNA.

The most common adverse events in the 12- and 8-week treatment arms included headache (14% and 17%, respectively); fatigue (12% and 15%); and nausea (15% and 9%).

The open-label, single-arm OPTIMIST-2 trial investigated the efficacy and safety of SMV/SOF in treatment-naive and treatment-experienced genotype-1 CHC patients with cirrhosis. The study’s primary endpoint was SVR12 with SMV/SOF compared with a historical control.

Twelve weeks of treatment with SMV/SOF resulted in an SVR12 rate of 84% (n = 86/103), which was superior to the SVR12 rate of 70% in the control group. Higher SVR12 rates were observed in patients with baseline NS5A polymorphisms with or without NS3 Q80K polymorphisms (100%; n = 13/13); in patients with albumin greater than or equal to 4 g/dL (94%; n = 47/50); and in treatment-naïve patients (88%; n = 44/50). The most common adverse events included fatigue (20%), headache (20%), and nausea (11%).

Hepatitis C affects approximately 2.7 million people in the U.S. and is a leading cause of chronic liver disease. Approximately 150 million people are infected with hepatitis C worldwide, and 350,000 people die each year from the disease globally. When left untreated, hepatitis C can cause significant liver damage, including cirrhosis. In addition, hepatitis C may increase the risk of developing complications from cirrhosis, which may include liver failure.

Source: Pipeline Review; July 24, 2015.

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