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AASLD 2012: Telaprevir Twice-daily Works as Well as Every 8 Hours, Safe for Hep C Patients with Cirrhosis

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The HCV protease inhibitor telaprevir (Incivek) taken twice-daily with pegylated interferon plus ribavirin is as likely to produce sustained virological suppression as the approved 3-times-daily schedule, with similar safety and tolerability even for people with advanced liver fibrosis, according to study findings presented last week at the American Association for the Study of Liver Diseases Liver Meeting (AASLD 2012) in Boston.

The pivotal trials that supported approval of the HCV protease inhibitors telaprevir and boceprevir (Victrelis) -- the first direct-acting antiviral agents for hepatitis C treatment -- administered both drugs every 8 hours. But this dosing regimen is inconvenient for patients, which may result in missed doses and reduced effectiveness.

Maria Buti from Hospital Vall d'Hebron in Barcelona and colleagues conducted the Phase 3 open-label OPTIMIZE trial comparing telaprevir twice-daily versus every 8 hours, to see if the less frequent dosing schedule is non-inferior to the approved regimen.

OPTIMIZE enrolled 740 previously untreated patients with genotype 1 chronic hepatitis C, mostly in North America and Europe. About 60% were men, more than 90% were white, and the mean age was 48 years. Nearly 60% had harder-to-treat HCV subtype 1a and about 70% had non-favorable IL28B gene variants. About 30% had advanced liver disease (stage F3-F4), including 14% with cirrhosis.

Participants were randomly assigned (1:1) to received telaprevir either at doses of 750 mg every 8 hours (Q8H) or 1125 mg every 12 hours (BID), both in combination with pegylated interferon alfa-2a (Pegasys) and 1000-1200 mg/day weight-adjusted ribavirin.

Results

  • Similar proportions of participants in the 2 arms -- 73% on Q8H telaprevir and 74% on BID -- achieved sustained virological response 12 weeks after completing treatment (SVR12) in an intent-to-treat analysis.
  • In a per-protocol or as-treated analysis, response rates remained similar, 75% and 76%, respectively.
  • Proportions of patients with rapid virological response (RVR) at week 4 who went on to achieve SVR12 were also similar, 85% and 86%, respectively.
  • On-treatment virological breakthrough rates were the same in both arms.
  • Response rates did not differ significantly between Q8H and BID dosing for any patient subgroup based on IL28B status or fibrosis stage.
  • For patients with cirrhosis, SVR12 rates were 49% and 54%, respectively.
  • Nearly 100% of people in both study arms experienced some adverse events.
  • However, rates of serious adverse events (9% and 8%, respectively) and adverse events leading to telaprevir discontinuation (19% vs 15%, respectively) were similar in both arms.
  • About half of participants in both the Q8H and BID arms developed rash.
  • The rate of grade 3 or higher anemia was somewhat higher in the BID arm (19% vs 26%), but the difference was not statistically significant.

"In this study, with a high proportion of patients with bridging fibrosis or compensated cirrhosis, the efficacy of 1125 mg BID telaprevir was non-inferior to 750 mg Q8H, offering the potential of simplified dosing to genotype 1 HCV-infected patients," the researchers concluded. "Safety and tolerability were generally similar between regimens and consistent with the known profile of telaprevir."

11/20/12

Reference

M Buti, K Agarwal, YJ Horsmans, et al. OPTIMIZE trial: Non-inferiority of twice-daily telaprevir versus administration every 8 hours in treatment-naïve, genotype 1 HCV infected patients. 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2012). Boston, November 9-13, 2012. Abstract LB-8.

Other Source

Vertex Pharmaceuticals. Vertex Presents New Phase 3 Data that Showed People with Hepatitis C Treated with Twice-Daily Telaprevir Achieved Viral Cure (SVR12) Rates Similar to Those Treated Three Times Daily. Press release. November 10, 2012.