From: "U.S. Food & Drug Administration (FDA)" <fda@xxxxxxxxxxxxxxxxxxxxxxx>
Date: Tue, 01 Mar 2016 15:13:14 -0600
Title: Olysio label revised
Informationabout FDA Hepatitis product approvals, safety warnings, medical product labeling changes, notices of upcoming public meetings, and notices about proposed regulatory guidances.
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
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