Telaprevir is effective against genotype 2, but not genotype 3
Telaprevir Effective for Genotype 2 But Not For Genotype 3
EASL April 23-26 2009
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-NAIVE 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-naIve 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 (LOD1-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.
Hey Ags how you doing?
They are hoping for next year still..........so are we! Keep your fingers crossed!
Doing pretty good girl. hopefully this lousy disease will be eradicated in the next 5-10 yrs. Just finished building a beautiful beach house with a great view. Hope my liver holds out because I want to be sitting on my deck relaxing for alot of years. I want to say thank you for answering all of us out here who are still struggling with this monster, you always seem to be there for me.