AASLD: High SVR Rates Seen with Telaprevir for Hepatitis C

AASLD: High SVR Rates Seen with Telaprevir for Hepatitis C
By John Gever, Senior Editor, MedPage Today
Published: November 06, 2009
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit
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Action Points

* Explain to interested patients that pegylated interferon and ribavirin for 48 weeks is the standard treatment for HCV infection and there is no established alternative treatment for patients with suboptimal response to this therapy.


* Explain that telaprevir is not FDA approved for any purpose and is available only in a clinical trial setting.


* Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered preliminary until published in a peer-reviewed journal.

BOSTON -- Availability of direct antiviral drugs for hepatitis C virus (HCV) infection moved another step closer to realization, with favorable results reported here for the investigational drug telaprevir in two Phase II studies.

In a trial with patients who had failed to obtain satisfactory responses to pegylated interferon and ribavirin (Rebetol), sustained virologic responses were seen in up to 53% of patients who had telaprevir added to the two standard drugs, reported John G. McHutchison, MD, of Duke University.

And another study, in which the drug was given twice a day (along with interferon and ribavirin) instead of the three-times-daily regimen used in other telaprevir trials, found sustained virologic response rates upwards of 80% in treatment-naive patients, said Patrick Marcellin, MD, of Beaujon Hospital in Clichy, France.

Both trials were reported here at the American Association for the Study of Liver Diseases annual meeting.

Telaprevir is one of several HCV protease inhibitors making their way through the development pipeline. Along with a similar drug called boceprevir, it is the most advanced, with Phase III studies now underway.

They're widely expected to be the first direct antiviral drugs made available for HCV, with FDA approval possible in 2011.

McHutchison presented data from a study called PROVE3 that randomized 453 patients with HCV genotype 1 to one of four treatments, three of which included telaprevir.

Patients in PROVE3 had received a previous course of treatment with interferon and ribavirin but either did not have viral loads reduced to undetectable levels or relapsed following an initial response.

The best sustained virologic response rates in the trial were seen with the two regimens that combined telaprevir with interferon and ribavirin.

In one, patients received telaprevir for 12 weeks and interferon and ribavirin for 24 weeks; the other regimen provided telaprevir for 24 weeks and interferon-ribavirin for 48 weeks.

Sustained virologic responses were obtained by 51% and 53% of patients in those groups, respectively, compared with 14% among patients given interferon and ribavirin for 48 weeks.

In the fourth group, treated with telaprevir and pegylated interferon for 24 weeks, and no ribavirin, the sustained response rate was 24%.

Rates for all three telaprevir regimens were significantly higher than the interferon-ribavirin control arm (P<0.03).

Patients who had had prior relapses did much better than those who had not responded at all to standard treatment, McHutchison said, with sustained response rates of up to 76% versus less than 40% for prior nonresponders.

McHutchison said viral breakthroughs during treatment were markedly higher with the regimen that included telaprevir but omitted ribavirin than with any of the other three.

He also said that when patients obtained sustained responses, they were maintained for an additional 24 weeks in nearly every case.

All the telaprevir regimens in PROVE3 gave the drug three times a day, but Marcellin reported results from another trial that tested a twice-daily schedule.

Dubbed C208, the 161-patient randomized study compared two regimens in which the drug was given every eight hours to two regimens with telaprevir given every 12 hours.

All four treatments also included pegylated interferon and ribavirin. Telaprevir was given for 12 weeks in all treatment arms, with interferon and ribavirin continued for 12 or 36 additional weeks depending on virologic response.

Patients were previously untreated and were infected with HCV genotype 1.

Marcellin reported virtually identical sustained virologic response rates for all four treatment arms, from 81% to 85%.

Some patients received pegylated interferon-alfa-2a (Pegasys) and some received the alfa-2b version (PEGIntron), but sustained response rates did not differ between these forms of interferon.

Response rates at treatment week four also did not differ markedly between treatment groups, and did not differ at all between the eight-hour and 12-hour dosing schedules.

Patients receiving the alfa-2a form had rapid response rates of about 80%, whereas just under 70% of those receiving the alfa-2b version had responses at week four.

In both studies, anemia and skin rashes and pruritus were relatively common. McHutchison reported that 18 patients in the three telaprevir arms in PROVE3 discontinued treatment because of the skin problems, whereas there were no discontinuations in the standard-of-care group for those symptoms.

Three patients withdrew because of anemia, which also drove one patient in the interferon-ribavirin arm out of the study.

However, with 350 patients in the three telaprevir arms, the rate of discontinuations was not unusually high, McHutchison suggested. The numbers and types of adverse events "were similar to those reported in prior Phase II studies," he said.

Marcellin said rashes, pruritus, and anemia each affected about half of patients in each treatment group, with no difference between the eight-hour and 12-hour dosing groups.

Scott Friedman, MD, president of AASLD and a hepatologist at Mount Sinai School of Medicine in New York City, said the PROVE3 results were especially compelling.

He said treatments for patients who fail or relapse with standard interferon-ribavirin therapy are currently lacking.

"I have a lot of patients who have tried and failed, and they're desperate for therapy," he said. "From a practical perspective, these are the patients we're anxious to help."

Both studies were funded by Vertex and Tibotec, developers of telaprevir.

McHutchison reported relationships with Abbott, Anadys, Biolex, Gilead, National Genetics Institute, Pharmasset, Pfizer, United Therapeutics, GlaxoSmithKline, Globimmune, Human Genome Sciences, Idera, Intarcia, Medtronic, Novartis, Roche, Schering-Plough, Vertex, Virochem, and Osiris. Some co-authors were employees of Vertex.

Marcellin reported relationships with Roche, Schering-Plough, Gilead, Bristol-Myers Squibb, GlaxoSmithKline, Wyeth, and Indenix. Some co-authors were employees of Tibotec.

Friedman reported relationships with Exalenz, sanofi-aventis, Axcan, Angion, Intercept, 7TM, Stromedix, and Celera.

Primary source: Hepatology
Source reference:
McHutchison J, et al "PROVE3 Final results and 1-year durability of SVR with telaprevir-based regimen in hepatitis C genotype 1-infected patients with prior non-response, viral breakthrough or relapse to peginterferon-alfa-2a/b and ribavirin therapy" Hepatology 2009; 50: 334A-5A.

Additional source: Hepatology
Source reference:
Marcellin P, et al "Virological analysis of patients receiving telaprevir administered q8h or q12h with peginterferon-alfa-2a or -alfa-2b and ribavirin in treatment-naïve patients with genotype 1 hepatitis C: Study C208" Hepatology 2009; 50: 395A.