AASLD: Telaprevir Yields Good Response in Combo Therapy for HCV

BOSTON, Nov. 7 -- A regimen containing the investigational protease inhibitor telaprevir in combination with a pegylated interferon and ribavirin appears to produce sustained viral responses in two-thirds of patients with hepatitis C (HCV) infections, said U.S. and European investigators.
Action Points
Explain to patients that there are effective therapies for the treatment of hepatitis C infection, and encourage those who may be at risk to be tested.
Explain that telaprevir is an investigational agent and has not yet been approved by the FDA for treatment of HCV.
Note that this study was published as an abstract and presented at a conference. The data and conclusions should be considered to be preliminary until published in a peer-reviewed publication.
At 24 weeks, 61% of patients infected with HCV genotype 1 had a sustained viral response (SVR) in the PROVE1 (U.S.) trial, and 65% had an SVR in the European PROVE2 study.
Interim analyses of data from the ongoing phase IIb trials were reported at the American Association for the Study of Liver Diseases meeting here by Christophe Hezode, M.D., of the Hôpital Henri Mondor, in Creteil, France, for the PROVE2 investigators, and Ira M. Jacobson, M.D., of Weill Medical College of Cornell University, for the PROVE1 investigators.
In both of the PROVE studies, patients were randomized into one of four arms. In PROVE1, three groups received telaprevir 750 mg every 8 hours, pegylated interferon alpha 2a (Peg-IFN) 180 μg/week, plus ribavirin (Rebetol) 1,000 to 1,200 mg/day for 12 weeks.
One of the three groups received no additional therapy, one received 12 additional weeks of Peg-IFN and ribavirin, and one received 36 additional weeks. Controls received up to 48 weeks of Peg-IFN and ribavirin, with no telaprevir.
In PROVE2, patients received telaprevir-based regimens for 12, 24, or 48 weeks, compared with 48 weeks of Peg-IFN and ribavirin for controls. In one of the telaprevir arms, patients received the protease inhibitor plus Peg-IFN but no ribavirin for 12 weeks.
Baseline patient characteristics in PROVE1 were similar across telaprevir treatment and control arms. The median HCV RNA (by Roche Taqman assay) at entry was similar across all arms, and 87% of patients had a high viral load, defined as greater than 800,000 IU/mL. The mean patient age was 49 (range 21 to 63), and the mean weight was 82.1 kg (range 46 to 136).
The PROVE2 patient parameters at baseline were similar to those of the patients in the PROVE1 study.
Rates of SVR at 24 weeks among patients in the 12-week treatment arm with ribavirin were 35% in PROVE1 and 59% in PROVE2.
The SVR rate in the 12-week telaprevir plus Peg-IFN without ribavirin arm in PROVE2 was 29%.
Sustained viral response results from the control arms of PROVE1 and PROVE2 were not available, the presenters said, but noted that, at the time of the interim analysis, 45% of controls in PROVE1 had undetectable HCV RNA (10 IU/mL) at the end of treatment (48 weeks of standard Peg-IFN plus ribavirin).
In PROVE2, 59% of controls, who received the same regimen as controls in PROVE1, had undetectable HCV RNA at week 36 of treatment.
Dr. Jacobson said that among those patients who achieved a rapid virologic response and had data available for an SVR analysis, 91% had an SVR at 12 weeks.
Data from the combined studies showed that viral breakthrough occurred in 5% of patients who received telaprevir during the first 12 weeks of treatment. Most viral breakthroughs occurred in the first month of treatment, and were generally associated with low blood levels of interferon, Dr. Jacobson said.
The combined relapse rate for patients who completed 24 weeks of treatment was 9%. Among those patients who had a rapid virologic response and completed 24 weeks of therapy, viral relapse occurred in 7% during the post-treatment period.
The adverse events occurring significantly more frequently among telaprevir-treated patients compared with controls included gastrointestinal disorders, rash, pruritus, and anemia.
In the U.S., 18% of all patients on telaprevir for 12 weeks discontinued therapy, compared with 3% of controls. After week 12, discontinuations because of adverse events were 8% in both the telaprevir and control arms.
In PROVE2, the overall discontinuation rate through 12 weeks was 14% across all telaprevir treatment arms and 6% in the control arm.
"Combination therapy including, for example, telaprevir as a targeted protease inhibitor has the very high potential to increase sustained virologic response rate above current regimens by also decreasing the overall duration of therapy," Dr. Hezode said.
Following the presentation of the PROVE1 data, Dr. Jacobson was asked by Jay M. Hoofnagle, M.D, from the National Institute of Diabetes and Digestive and Kidney Disease, why the viral response rates were not higher among controls.
"It's a little bit discouraging that you only got a 65% end-of-treatment response [with telaprevir regimens]," Dr. Hoofnagle said. "Frankly, that's what you get with genotype 1 with most studies of Peg and ribavirin…You keep reporting data from this trial and the patients in the trial are still in the trial, so you've ruined the blind and the objectivity of the trial by continually reporting the data, and I think that's why you have such a bad result in the control group."
The PROVE1 and PROVE2 investigators plan to present results of another analysis of the trial in 2008.
The study was funded by Vertex, maker of telaprevir. Dr. Jacobson and Dr. Hezode have received grant and research support from the company.
Primary source: American Association for the Study of Liver DiseasesSource reference: Zeuzem S, et al "PROVE2: Phase II Study of VX950 (TELAPREVIR) in Combination with Peginterferon ALFA2A With or Without Ribavirin in Subjects With Chronic Hepatitis C, First Interim Analysis" AASLD Meeting 2007; Abstract 80 presented Nov. 5. Additional source: American Association for the Study of Liver DiseasesSource reference: Jacobson IM, et al "Interim Analysis Results from a Phase 2 Study of Telaprevir with Peginterferon alfa-2A and Ribavirin in Treatment naïve Subjects with Hepatitis C" AASLD Meeting 2007; Abstract 177 presented Nov. 6.