Telaprevir for Genotype 2/3

Telaprevir for Genotype 2/3

EASL April 23-26 2009
Copenhagen, Denmark
Reported by Jules Levin

In phase IIb studies in treatment-naives, mostly caucasians, telaprevir in combination with peg/RBV improved SVR rates in half the time of treatment compared with standard of care:

--PROVE1: 61% vs 41% (p=0.02)
--PROVE2: 69% vs 46% (p=.004)

In this study genotype 2 treatment naive patients achieved a mean 4 log reduction in viral load after 6 days on monotherapy with telaprevir. The triple combination of telaprevir + peg/RBV achieved a mean 5.3 log reduction in viral load at day 16. But genootype 3 patients only achieved a -.80 reduction in viral load so therapy for genotype 3 won't be pursued.

ACTIVITY OF TELAPREVIR ALONE OR IN COMBINATION WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN TREATMENT-NAÏVE GENOTYPE 2 AND 3 HEPATITIS-C PATIENTS: INTERIM RESULTS OF STUDY C209

G.R. Foster1, C. Hezode2, J.-P. Bronowicki3, G. Carosi4, O. Weiland5, L. Verlinden6, R. van Heeswijk6, T. Vangeneugden6, G. Picchio7, M. Beumont-Mauviel6

1Barts and The London School of Medicine, Institute of Cellular and Molecular Science, London, UK, 2Hôpital Henri-Mondor, AP-HP, Université Paris XII, Créteil, 3Centre Hospitalier Universitaire de Nancy, Vandoeuvre-lès-Nancy, France, 4Clinic of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy, 5Karolinska University Hospital Huddinge, Stockholm, Sweden, 6Tibotec BVBA, Mechelen, Belgium, 7Tibotec Inc., Yardley, PA, USA

Background: Telaprevir (TVR) produces rapid and consistent reductions of HCV-RNA plasma levels in G1 patients. Study C209 is an ongoing, partially blinded, randomized, Phase-2a study of TVR, administered alone or with peginterferon-alfa-2a (Peg-IFN) and ribavirin (RBV), investigating early viral kinetics of HCV-RNA decay in treatment-naïve subjects with genotype 2/3 (G2/3) infection. We report the results of the primary analysis conducted after 15 days of treatment.

Methods: 49 subjects were randomized to receive 15 days of either TVR 750mg q8h alone (armA;G2/3;n=10/8), TVR 750mg q8h with Peg-IFN 180µg/week and RBV 800mg/day (armB;G2/3;n=5/9), or Peg-IFN 180µg/week and RBV 800mg/day plus placebo (armC;G2/3;n=8/9) . Viral load was measured using Taqman assay (LOD< 10 IU/mL). Viral breakthrough (vBT) was defined as >1-log increase in HCV-RNA above nadir or >100 IU/mL HCV-RNA after previously undetectable HCV-RNA. An ITT analysis was performed when all treated subjects had completed 15 days of dosing or discontinued earlier.

Results: Mean baseline log10 HCV-RNA was 6.45 and 6.44 IU/mL among G2- and G3-infected subjects, respectively.

The mean (SE) log10 changes in HCV-RNA at days 3/15 in G2-infected subjects were -3.0(0.37)/-3.1(0.64), -3.9(0.23)/-5.3(0.27), and -2.2(0.56)/-4.0(0.70) and in G3-infected subjects -0.8(0.33)/-0.5(0.11), -2.9(0.24)/-4.7(0.32), and -2.6(0.40)/-4.5(0.36) for arms A, B, and C, respectively.

The mean (SE) log10 maximum HCV RNA change in G2/G3-infected subjects was -4.0(0.49)/-0.8(0.33), -5.5(0.24)/-4.7(0.32) and -4.0(0.70)/-4.5(0.36) for arms A, B and C, respectively. In G3-infected subjects, responses varied across subtypes. The proportion of G2/G3-infected subjects with undetectable HCV-RNA at day15 was 0%/0%, 40%/22% and 25%/11% for arms A, B and C, respectively. Among G2/G3 subjects receiving TVR monotherapy, 6 and 5 patients, respectively, developed a vBT by day15; no vBTs were observed in arms B or C. Overall incidence of AEs was similar across arms and the most common AEs in TVR arms were rash-related events, nausea, and influenza-like illness, in line with previous reports. One patient in arm B discontinued therapy due to rash. No SAEs were reported in this trial.

Conclusions: TVR demonstrated substantial antiviral activity against HCV G2, while its activity against G3 was limited. These findings support additional investigation of TVR for the treatment of G2 HCV infection.