Bob Roehr

November 08, 2010

November 8, 2010 (Boston, Massachusetts) — Treatment of hepatitis C virus (HCV) infection with the protease inhibitor telaprevir added to a standard of care regimen of pegylated interferon alfa-2a plus ribavirin can be shortened from 48 weeks to 24 weeks in patients with an extended rapid viral response (eRVR), according to data presented here at The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting.

ILLUMINATE was a multicenter phase 3 open-label study in genotype 1 treatment-naïve patients that used guided duration of treatment to determine the length of the regimen. Principal investigator Kenneth E. Sherman, MD, from the University of Cincinnati College of Medicine in Ohio, delivered the results.

Patients received 12 weeks of telaprevir (750 mg every 8 hours) added to peginterferon alfa-2a (180 μg/week) and weight-based ribavirin (standard of care). Those who achieved an eRVR (undetectable HCV RNA at weeks 4 and 12) were randomized at week 20 to receive an additional 4 weeks or 28 weeks of telaprevir plus standard of care, for a total of 24 or 48 weeks of treatment. Patients who did not meet the eRVR criteria received a standard 48-week course of therapy.

The primary end point was sustained virologic response (SVR) below 25 copies/mL (TaqMan assay) 24 weeks after completion of the regimen. The margin of noninferiority was predefined as –10.5% on intent-to-treat analysis.

Dr. Sherman said stopping rules included discontinuation of telaprevir in those who had HCV RNA levels above 1000 copies/mL at week 4 and continuation of standard of care.

At week 12, "those who failed to achieve at least a 2 log drop from baseline were discontinued on all study drugs and classified as a nonresponders. Between weeks 24 and 36, any patient with a detectable HCV RNA level discontinued all study drugs."

ILLUMINATE involved 540 patients. Of these, 100 discontinued treatment for a variety of reasons before reaching week 20, when randomization was done.

In all, 322 (65%) achieved eRVR (72% on intent-to-treat analysis) and were randomized to either 24 or 48 weeks of telaprevir treatment. SVR was achieved in 92% and 88%, respectively, Dr. Sherman reported.

"There was a positive 4.5% increase in the shorter therapy period; clearly, that was within the noninferiority range," he added. There was no statistical difference between the 2 groups in terms of relapse.

Turning to factors that traditionally predict a poorer response, Dr. Sherman said patients with hepatic fibrosis and cirrhosis showed "quite a respectable 63%" in SVR. "Among those who achieved eRVR, there was no difference between the groups, and no difference between 24 and 48 weeks of therapy," he reported.

There continues to be differences in responses along the lines of race/ethnicity, "but among those who achieved eRVR, there was no difference in response based on race or ethnicity."

Adverse events were those commonly seen in patients treated with the backbone of interferon and ribavirin. Rash attributed to telaprevir was a principle difference, with 63% of patients experiencing some degree of rash and 7% experiencing severe rash. It resolved upon discontinuation or completion of telaprevir. Discontinuation of all drugs for all causes was 7%; rash and anemia each caused 1% of discontinuations.

"Overall, due to any adverse event, 12% discontinued use of telaprevir; rash events constituted 7% and anemia events 2%," he said. There was a 17% discontinuation of all drugs because of adverse events. The rates were similar to those seen in other phase 2 and 3 trials of telaprevir.

Dr. Sherman concluded that there was "no clinical benefit to extending telaprevir-based therapy beyond 24 weeks in patients with eRVR, [which comprised] two thirds of the study patients. All study patients, regardless of liver fibrosis stage, race, or ethnicity, achieved high SVR rates with response-guided therapy."

In response to a question on resistance from the audience, he said that "breakthrough was observed in 1% to 3% of patients who were in the eRVR groups. The resistance patterns are similar to what has been seen previously in patients who do not ultimately clear" the virus, Dr. Sherman responded.

Conference chair Arun Sanyal, MD, from the Medical College of Virginia in Richmond, called the rates of response "incredible when you think about the time when we only had a 5% response rate to interferon." It represents another big step forward in our ability to treat HCV infection, he asserted.

Vertex/Johnson & Johnson sponsored the ILLUMINATE study. Dr. Sherman reports research funding and consulting ties to the company. Dr. Sanyal reports research and consulting ties to other companies developing HCV drugs.

The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting: Abstract LB-2 Presented November 1, 2010.

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