General Information

Olysio (simeprevir) is a small molecule orally active inhibitor of the NS3/4A protease of hepatitis C virus.

Olysio is specifically indicated for the treatment of chronic hepatitis C infection as a component of a combination antiviral treatment regimen.

Olysio is supplied as a capsule for oral administration. The recommended dose is one 150 mg capsule taken once daily with food. Olysio should be administered with both peginterferon alfa and ribavirin. The recommended treatment duration of Olysio with peginterferon alfa and ribavirin is 12 weeks, followed by either 12 or cc36 additional weeks of peginterferon alfa and ribavirin depending on prior response status.

Clinical Results

FDA Approval
The FDA approval of Olysio was based on the following trials:
Treatment-Naïve Adult Subjects with HCV Genotype 1 Infection
Two randomized, double-blind, placebo-controlled, 2-arm, multicenter, trials (QUEST 1 and QUEST 2) were conducted The design of both trials was similar. All subjects received 12 weeks of once daily treatment with 150 mg Olysio or placebo, plus Peg-IFN-alfa-2a (QUEST 1 and QUEST 2) or Peg-IFN-alfa-2b (QUEST 2) and RBV, followed by 12 or 36 weeks of therapy with Peg-IFN-alfa and RBV in accordance with the on-treatment protocol-defined RGT criteria. Subjects in the control groups received 48 weeks of Peg-IFN-alfa-2a or -2b and RBV alone. In the pooled analysis of QUEST 1 and QUEST 2, 88% (459/521) of Olysio-treated subjects were eligible for a total treatment duration of 24 weeks. In these subjects, the SVR12 rate was 88% (405/459). Seventy-eight percent (78%; 404/521) of Olysio-treated subjects had undetectable HCV RNA at Week 4 (RVR); in these subjects the SVR12 rate was 90% (362/404), while 8% (32/392) with undetectable HCV RNA at end of treatment had viral relapse. SVR12 rates were higher for subjects receiving Olysio with Peg-IFN-alfa-2a or Peg-IFN-alfa-2b and RBV (88% and 78%, respectively) compared to subjects receiving placebo with Peg-IFN-alfa-2a or Peg-IFN-alfa-2b and RBV (62% and 42%, respectively) (QUEST 2).
Adult Subjects with HCV Genotype 1 Infection who Failed Prior Therapy
A randomized, double-blind, placebo-controlled, 2-arm, multicenter, phase II trial, PROMISE, was conducted in subjects with HCV genotype 1 infection who relapsed after prior IFN-based therapy. All subjects received 12 weeks of once daily treatment with 150 mg Olysio or placebo, 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 the protocol-defined RGT criteria. Subjects in the control group received 48 weeks of Peg-IFN-alfa-2a and RBV alone. In PROMISE, 93% (241/260) of Olysio-treated subjects were eligible for a total treatment duration of 24 weeks. In these subjects, the SVR12 rate was 83% (200/241). Seventy-seven percent (77%; 200/260) of Olysio-treated subjects had undetectable HCV RNA at Week 4 (RVR); in these subjects the SVR12 rate was 87% (173/200), while 13% (25/196) with undetectable HCV RNA at end of treatment had viral relapse. A second randomized, double-blind, placebo-controlled, 7-arm, phase IIb trial, ASPIRE, was also conducted. ASPIRE enrolled subjects with HCV genotype 1 infection, who failed prior therapy with Peg-IFN-alfa and RBV (including prior relapsers, partial responders or null responders). Subjects received 12, 24 or 48 weeks of 100 mg or 150 mg Olysio in combination with 48 weeks of Peg-IFN-alfa-2a and RBV, or 48 weeks of placebo in combination with 48 weeks of Peg-IFN-alfa-2a and RBV. In prior partial responders, SVR24 rates in subjects receiving Olysio with Peg-IFN-alfa and RBV were 47% and 77% in subjects with HCV genotype 1a and 1b, respectively, compared to 13% and 7%, respectively, in subjects receiving placebo with Peg-IFN-alfa and RBV. In prior null responders, SVR24 rates in subjects receiving OLYSIO with Peg-IFN-alfa and RBV were 41% and 47% in subjects with HCV genotype 1a and 1b, respectively, compared to 0% and 33%, respectively, in subjects receiving placebo with Peg-IFN-alfa and RBV.