FDA Update - OLYSIO (simeprevir) label revised to include pharmacokinetic, safety and efficacy data in treatment-naïve adult patients of East Asian ancestry with chronic hepatitis C virus genotype 1 infection.

OLYSIO 

The OLYSIO (simeprevir) label was updated to include pharmacokinetic, safety and efficacy data in treatment-naïve adult patients of East Asian ancestry with chronic hepatitis C virus genotype 1 infection.

Patients of East Asian ancestry exhibit higher simeprevir plasma exposures but no dosage adjustment is required based on race.

In a Phase 3 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 to non Asian HCV infected subjects in a pooled Phase 3 population from global trials

Adverse Reactions in East Asian Subjects

OLYSIO in combination with Peg IFN alfa and RBV was studied in a Phase 3 trial conducted in China and South Korea in treatment naïve subjects with chronic HCV genotype 1 infection (TIGER). The safety profile of OLYSIO in East Asian subjects was similar to that of the pooled Phase 3 population from global trials; however, a higher incidence of the laboratory abnormality hyperbilirubinemia was observed in patients receiving 150 mg OLYSIO plus Peg IFN alfa and RBV compared to patients receiving placebo plus Peg IFN alfa and RBV. Elevation of total bilirubin (all grades) 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. The bilirubin elevations were not associated with increases in liver transaminases and were reversible after the end of treatment.

Treatment Naïve East Asian Subjects with HCV Genotype 1 Infection

TIGER was a Phase 3, randomized, double blind, placebo controlled trial in HCV genotype 1 infected treatment naïve adult subjects from China and South Korea.

In this trial, 152 subjects received 12 weeks of once daily treatment with 150 mg OLYSIO plus Peg IFN alfa 2a and RBV, followed by 12 or 36 weeks of therapy with Peg IFN alfa 2a and RBV in accordance with protocol defined RGT criteria; and 152 subjects received 12 weeks of placebo plus Peg IFN alfa 2a and RBV, followed by 36 weeks therapy with Peg IFN alfa 2a and RBV. These 304 subjects had a median age of 45 years (range: 18 to 68 years; with 2% above 65 years); 49% were male; all were East Asians (81% were enrolled in China, and 19% in South Korea); 3% had a body mass index (BMI) greater or equal to 30 kg/m2; 84% had baseline HCV RNA levels greater than 800000 IU/mL; 82% had METAVIR fibrosis score F0, F1 or F2, 12% METAVIR fibrosis score F3, and 6% METAVIR fibrosis score F4 (cirrhosis); 1% had HCV genotype 1a, and 99% HCV genotype 1b; less than 1% of the overall population had Q80K polymorphism at baseline; 79% had IL28B CC genotype, 20% IL28B CT genotype, and 1% IL28B TT genotype. Demographics and baseline characteristics were balanced across the OLYSIO 150 mg and placebo treatment groups.

SVR12 rates were 91% (138/152) in the OLYSIO 150 mg treatment group and 76% (115/152) in the placebo treatment group

You can view the complete label at drugs@fda or dailymed.

Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration

Kimberly Struble
Division of Antiviral Products
Food and Drug Administration

Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration

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