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| |  Telaprevir-Based Therapy Provides High Rapid Viral Response in Treatment-Naive Patients With Genotype 1 Hepatitis C Virus: Presented at EASL By Emma Hitt, PhD MILAN, Italy -- April 29, 2008 -- Telaprevir in combination with pegylated interferon alfa-2a (PEG-IFN) and ribavirin resulted in a high rapid viral response (RVR) rate compared with PEG-IFN plus ribavirin alone when treating patients with genotype 1 hepatitis C virus (HCV-1). These interim findings, from the phase 2 PROVE 1 and PROVE 2 trials, were presented here at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL). The two trials are similar (although not identical) in design, with the exception that PROVE 1 is being conducted at 37 clinical centres in the United States, and PROVE 2 is being conducted at 28 centres in Europe. On April 24, John McHutchison, MD, Associate Director, Duke Clinical Research Institute, Durham, North Carolina, reported the findings from PROVE 1, in which 250 patients were randomised to 1 of 4 treatment arms. In group A (control arm), 75 patients were treated with PEG-IFN 180 µg/week, ribavirin 1000 to 1200 mg/day, and placebo for 48 weeks. The 3 experimental arms each received 12 weeks of telaprevir 750 mg 3 times per day, as well as PEG-IFN plus ribavirin for 48 weeks, 24 weeks, and 12 weeks in groups B (n = 79), C (n = 79), and D (n = 17), respectively. All groups were followed for 24 weeks after treatment had been stopped. At weeks 4 and 12, the proportion of patients achieving undetectable hepatitis C virus ribonucleic acid (HCV RNA) (limit of detection: 10 IU/mL) was higher in all groups compared with the control group. At week 4 (indicative of rapid viral response rate) HCV RNA was undetectable in 79% of telaprevir-treated patients versus 11% of the control subjects; at week 12, HCV RNA was undetectable in 70% versus 39% of patients, respectively. Similarly, the sustained viral response (SVR) was significantly higher with telaprevir: 61% and 67% in the 24- and 48-week telaprevir-based treatment arms, respectively, versus only 41% of patients receiving PEG-IFN plus ribavirin alone. Telaprevir more often was associated with adverse events leading to discontinuations (13% vs 3% in the control group). The incidences of rash and anaemia were higher in patients receiving telaprevir, and serious adverse events were reported in 11.4% of patients receiving telaprevir versus 5.3% in the control arm. Geoffrey Dusheiko, MD, Professor of Medicine, Royal Free Hospital and School of Medicine, London, United Kingdom, reported April 25 on the interim results of the PROVE 2 study -- a 4-arm, phase 2b clinical trial of 323 treatment-naive genotype 1 HCV-infected patients. This trial was similar in design to PROVE 1, except that ribavirin was excluded from the arm receiving 12 weeks of PEG-IFN and 12 weeks of telaprevir. The PROVE 2 study results also indicated that telaprevir combined with PEG-IFN with or without ribavirin produced significantly greater antiviral effect compared with PEG-IFN plus ribavirin. The SVR was 68% in the 24-week telaprevir arm and 62% in the 12-week arm, compared with 48% in the control arm. Adverse effects in PROVE 2 were comparable between the telaprevir-based treatments and the control arm, with the exception of a high incidence of rash, pruritus, and anaemia. Of patients in the telaprevir-based treatment arms, 13% discontinued treatment due to adverse events compared with 10% in the control arm. "The favourable risk-benefit profile supports further evaluation in the ongoing phase 3 study," said Dr. Dusheiko. "This regimen may lead to a new treatment approach for HCV genotype-1-infected patients," he added. The clinical utility of telaprevir will be evaluated further in the phase 3 ADVANCE trial, which will evaluate telaprevir in previously untreated patients with genotype 1 chronic HCV. The study will assess two 24-week telaprevir-based regimens versus a 48-week control arm, with a primary endpoint of SVR, at 24 weeks after the completion of treatment. Funding for the PROVE studies was provided by Vertex.
[Presentation title: PROVE1: Results From a Phase 2 Study of Telaprevir With Peginterferon Alfa-2a and Ribavirin in Treatment-Naïve Subjects With Hepatitis C. Abstract 4. Treatment of Chronic Hepatitis C With Telaprevir (TVR) in Combination With Peginterferon-Alfa-2a With or Without Ribavirin: Further Interim Analysis Results of the PROVE2 study. Abstract 58]
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