Home » Drug Information » FDA Approved Drugs » 2011
Medical Areas: Gastroenterology | Immunology | Hepatology (Liver, Pancreatic, Gall Bladder) | Infections and Infectious Diseases
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Vertex Pharmaceuticals
Approval Status: Approved May 2011
Treatment Area: genotype 1 chronic hepatitis C
Incivek (telaprevir) inhibits the hepatitis C protease NS3-4A, an enzyme that is essential for HCV viral replication.
Incivek is specifically indicated, in combination with peginterferon alfa and ribavirin, for the treatment of genotype 1 chronic hepatitis C (CHC) in adults with compensated liver disease, including cirrhosis, who are treatment-naïve or who have been previously treated with interferon-based treatment, including prior null responders, partial responders, and relapsers.
Invicek is supplied as a tablet for oral administration. The recommended dose is 750 mg (two 375-mg tablets) taken orally three times a day (7-9 hours apart) with food. Refer to the peginterferon alfa and ribavirin package inserts for instructions on dosing.
The FDA approval of Incivek was based on three clinical trials: two in treatment-naïve subjects and one in previously treated subjects (relapsers, partial responders, and null responders). In all three studies, Incivek was administered at a dosage of 750 mg every 8 hours; the peginterferon alfa-2a (Peg-IFN-alfa-2a) dose was 180 µg/week, and the ribavirin (RBV) dose was 1000 mg/day (subjects weighing less than 75 kg) or 1200 mg/day (subjects weighing greater than or equal to 75 kg).
Study 108 (ADVANCE)
This randomized, double-blind, parallel-group, placebo-controlled, trial enrolled 1,088 subjects. Incivek was given for the first 8 weeks of treatment (T8/PR regimen) or the first 12 weeks of treatment (T12/PR regimen) in combination with Peg-IFN-alfa-2a/RBV for either 24 or 48 weeks. Subjects who had undetectable HCV-RNA at weeks 4 and 12 (extended Rapid Virologic Response [eRVR]) received 24 weeks of Peg-IFN-alfa-2a/RBV treatment, and subjects who did not have undetectable HCV-RNA at weeks 4 and 12 (no eRVR) received 48 weeks of Peg-IFN-alfa-2a/RBV treatment. In the T8/PR group, the overall SVR rate was 72%. The eRVR rate was 57% and the SVR rate for eRVR subjects was 87%. The SVR rate for no eRVR subjects was 52%. More subjects in the T8/PR group experienced virologic breakthrough after Week 12 while receiving peginterferon alfa and ribavirin alone, 16% compared to 10% in T12/PR group. In addition, in the T12/PR group, 21 subjects had cirrhosis at baseline and the overall SVR in these subjects was 62%. Among subjects with cirrhosis, 43% achieved an eRVR and of those 78% achieved SVR. Twenty-six subjects were African Americans. The overall SVR among this population was 62%. Among these subjects, 31% achieved an eRVR and of those 89% (8/9) achieved SVR.
Study 111 (ILLUMINATE)
This randomized, open-label trial was designed to compare SVR rates in 540 subjects achieving eRVR who were treated with Incivek for 12 weeks in combination with Peg-IFN-alfa-2a/RBV for either 24 weeks (T12/PR24 regimen) or 48 weeks (T12/PR48 regimen). The SVR rate for all subjects enrolled in the trial was 74%. A total of 352 (65%) subjects achieved eRVR and of those 322 (60%) were randomized to 24 weeks (T12/PR24, n=162) or 48 weeks (T12/PR48, n=160) of treatment. The SVR rates were similar at 92% (T12/PR24) and 90% (T12/PR48), respectively. Sixty-one (11%) of subjects had cirrhosis at baseline. Among these subjects, 30 (49%) achieved an eRVR: 18 were randomized to T12/PR24 and 12 to T12/PR48. The SVR rates were 67% (12/18) for the T12/PR24 group and 92% (11/12) for the T12/PR48 group. African Americans comprised 14% of study subjects. Thirty-four (47%) African American subjects achieved an eRVR and were randomized to T12/PR24 or T12/PR48. The respective SVR rates were 88% (15/17) and 94% (16/17), compared to 93% (246/265) for Caucasians.
Previously Treated Adults
Study C216 (REALIZE)
This randomized, double-blind, placebo-controlled, trial enrolled 662 prior relapsers and prior non-responders who were randomized to one of two Incivek combination treatment groups (with and without a Peg-IFN-alfa-2a/RBV lead-in) or a control group. The T12/PR48 group received Incivek and Peg-IFN-alfa-2a/RBV for 12 weeks (without a lead-in), followed by placebo and Peg-IFN-alfa-2a/RBV for 4 weeks, followed by Peg-IFN-alfa-2a/RBV for 32 weeks. The T12(DS)/PR48 group had a lead-in (delayed start of Incivek) with placebo and Peg-IFN-alfa-2a/RBV for 4 weeks, followed by Incivek and Peg-IFN-alfa-2a/RBV for 12 weeks, followed by Peg-IFN-alfa-2a/RBV for 32 weeks. The Pbo/PR48 group received placebo and Peg-IFN-alfa-2a/RBV for 16 weeks, followed by Peg-IFN-alfa-2a/RBV for 32 weeks. Among prior relapsers, 76% achieved an eRVR and of those 95% achieved an SVR. In an earlier, dose-finding clinical trial, 78% of prior relapsers achieved an eRVR and were treated with 24 weeks of peginterferon alfa and ribavirin (T12/PR24); of those 94% (49/52) achieved an SVR. Twenty-three percent of Incivek-treated subjects had cirrhosis at baseline. SVR rates among cirrhotic subjects who received Incivek combination treatment compared to Pbo/PR48 were: 87% compared to 13% for prior relapsers, 34% compared to 20% for prior partial responders, and 14% compared to 10% for prior null responders. Four percent of treatment experienced subjects who received Incivek combination treatment were African Americans; the SVR rate for these subjects was 63% compared to 65% for Caucasians.
Adverse events associated with the use of Incivek may include, but are not limited to, the following:rashpruritusanemianauseahemorrhoidsdiarrhea anorectal discomfortdysgeusiafatiguevomitinganal pruritus
Mechanism of Action
Incivek is an inhibitor of the HCV NS3/4A serine protease, necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins and essential for viral replication.
For additional information regarding Incivek or hepatitis C, please visit the Incivek web page.