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Telaprevir Triple Therapy Shows Activity Against HCV Genotype 4


The HCV protease inhibitor telaprevir (Incivek or Incivo) in combination with pegylated interferon and ribavirin reduced viral levels by more than 4 log in people with genotype 4 hepatitis C in a short Phase 2a study, researchers reported in the September 15, 2013 Journal of Infectious Diseases.

The advent of direct-acting antiviral agents (DAAs) has brought about a new era of treatment for hepatitis C virus (HCV), enabling shorter-duration therapy with a higher likelihood of sustained virological response -- generally considered a cure. Second-generation agents now in development are more effective and better tolerated, and interferon-free regimens are on the horizon.

Most studies of new therapies for hepatitis C focus on HCV genotypes 1, 2, and 3. Genotype 1, the most common type in the U.S., is most difficult to treat with interferon. Genotypes 2 and 3 have traditionally been considered "easy to treat," but recent research indicates that genotype 2 is more responsive than genotype 3. Genotype 4 -- which is most common in the Middle East and North Africa but uncommon in the U.S. and Europe -- is sometimes lumped in with genotype 1 as "difficult-to-treat," but it has not been extensively studied in clinical trials of new therapies.

Yves Benhamou from Hôpital Pitié-Salpêtrière in Paris and an international team of colleagues conducted a randomized, partially blinded Phase 2a trial to evaluate telaprevir in previously untreated patients with genotype 4 chronic hepatitis C.

A total of 24 participants were randomly assigned to receive either 750 mg telaprevir as monotherapy every 8 hours, the same dose of telaprevir in combination with pegylated interferon alfa-2a (Pegasys) and ribavirin, or pegylated interferon/ribavirin plus placebo, all for 15 days, followed by pegylated interferon/ribavirin alone for 46 or 48 weeks.


  • HCV RNA levels decreased slightly after starting treatment with telaprevir monotherapy or pegylated interferon/ribavirin plus placebo.
  • In contrast, participants who received triple therapy with telaprevir plus pegylated interferon/ribavirin experienced rapid and substantial viral load drops.
  • At day 15, median HCV RNA reductions from baseline were -0.77 log IU/mL in the telaprevir monotherapy arm, -1.58 log IU/mL in the pegylated interferon/ribavirin/placebo arm, and -4.32 in the telaprevir triple therapy arm.
  • 1 patient on triple therapy, and none in the other 2 arms, achieved undetectable HCV viral load during this brief treatment period.
  • 5 of the 8 patients (63%) who received telaprevir monotherapy experienced viral breakthrough within 15 days of starting treatment, indicative of drug resistance.
  • Incidence of adverse events was similar across treatment arms, and comparable to rates seen in previous clinical trials of people with other HCV genotypes.
  • 1 participant in the telaprevir monotherapy arm experienced a serious adverse event, considered unrelated to telaprevir, which led to early treatment discontinuation.

"Telaprevir with [pegylated interferon/ribavirin] had greater activity than [pegylated interferon/ribavirin] treatment or telaprevir monotherapy against HCV genotype 4," the study authors concluded. "Telaprevir was generally safe and well tolerated."

"Further investigation of telaprevir combination therapy in patients with HCV genotype 4 infection is warranted," they recommended.



Y Benhamou, J Moussalli, V Ratziu, et al. Telaprevir Activity in Treatment-Naive Patients Infected Hepatitis C Virus Genotype 4: A Randomized Trial. Journal of Infectious Diseases 208(6):1000-1007. September 15, 2013.