The U.S. Food and Drug Administration has revised labeling for the hepatitis C drug Olysio (simeprevir) after adverse reactions were experienced by East Asian patients during a phase III trial.
Olysio, produced by Janssen Products LP, is a hepatitis C virus NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) genotype 1 or 4 infection as a component of a combination antiviral treatment regimen. It was initially approved by the FDA in November 2013.
The update was announced in a March 1 FDA Hepatitis Email Updates letter signed by Richard Klein and his colleagues at the FDA Office of Health and Constituent Affairs. The updated labeling comes as a result of a randomized, double-blind phase III trial (the TIGER trial) conducted in China and South Korea. Olysio, in combination with Peg interferon (IFN) -alfa and ribavirin (RBV), was studied in treatment-naive subjects with chronic HCV genotype 1 infection.
The TIGER investigators observed a higher incidence of the laboratory abnormality hyperbilirubinemia in trial subjects receiving 150 mg Olysio plus Peg IFN-alfa and RBV, compared with patients receiving placebo plus Peg IFN-alfa and RBV. Elevation of total bilirubin was observed in 66% (99/151) of subjects treated with 150 mg Olysio plus Peg IFN-alfa and RBV and in 26% (40/152) of subjects treated with placebo plus Peg IFN-alfa and RBV. Bilirubin elevations were mainly grade 1 or grade 2. Grade 3 elevations in bilirubin were observed in 9% (13/151) of subjects treated with 150 mg Olysio plus Peg IFN-alfa and RBV and in 1% (2/152) of subjects treated with placebo plus Peg IFN-alfa and RBV. There were no grade 4 elevations in bilirubin.
Importantly, the bilirubin elevations were not associated with increases in liver transaminases and were reversible after the end of treatment.
The new labeling on Olysio includes the following: “Patients of East Asian ancestry exhibit higher simeprevir plasma exposures, but no dosage adjustment is required based on race. In a phase III trial conducted in China and South Korea, the mean plasma exposure of simeprevir in East Asian HCV-infected subjects was 2.1-fold higher, compared with non Asian HCV-infected subjects in a pooled phase III population from global trials.”
To read the FDA labeling for Olysio, the email announcement suggests visiting the Drugs@FDA website or the DailyMed website managed by the National Library of Medicine. As of this writing, these sites have yet to be updated.
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