Clinical

Boceprevir effective against HCV in nonresponders and treatment-na�ve patients

Last Updated: 2010-11-02 17:37:24 -0400 (Reuters Health)

By Anne Harding

NEW YORK (Reuters Health) - Boceprevir produces a substantial improvement in sustained virologic response (SVR) rates among hepatitis C virus patients who have not responded to or relapsed after standard treatment - and in treatment-na�ve patients as well.

Based on data from two phase III trials presented this week in Boston at the annual meeting of the American Association for the Study of Liver Diseases, drugmaker Merck has begun submission of a New Drug Application for boceprevir to the US Food and Drug Administration and expects to complete regulatory submissions in the US and Europe in 2010.

The experimental drug is an oral inhibitor of HCV0NS3 protease. Dr. Bruce R. Bacon, a professor of internal medicine at the St Louis University School of Medicine in Missouri, presented the findings of one of the trials today. Both studies were done in genotype 1 patients, who represent about 75% of patients with hepatitis C, Dr. Bacon noted in comments to Reuters Health; among these patients, only 40% will be successfully treated with interferon and ribavirin.

In Merck's HCV RESPOND-2 trial, Dr. Bacon and his team randomly assigned 403 patients who had not responded to treatment with peg interferon alfa 2B and ribavirin, or had relapsed, to three protocols:

-- interferon and ribavirin for 48 weeks (Pegintron 1.5 mcg/kg/week and Rebetol 600-1,400 mg/day);

-- four weeks of these two drugs, after which patients also received "response-guided" therapy with 800 mg of boceprevir three times daily; or

-- the four-week interferon/ribavirin lead-in followed by the three-drug therapy for 44 weeks.

In the group receiving response-guided therapy, patients who were HCV-negative at week eight received 28 more weeks of interferon, ribavirin, and boceprevir. Patients who were still HCV-positive at eight weeks received 28 more weeks of all three drugs, followed by 12 weeks of ribavirin plus interferon.

At 24 weeks after the end of treatment, SVR rates were 21% in the control group, 59% in the response-guided therapy arm, and 66% in the third arm.

Three percent of patients in the control group discontinued due to adverse events, compared to 8% of patients in the second arm of the study and 12% in the third arm.

The most common side effects seen with boceprevir were dysgeusia and anemia. About 40 to 45% of patients had anemia with hemoglobin less than 10, Dr. Bacon added, similar to the rate seen with telaprevir, a linear protease inhibitor under development by Vertex Pharmaceuticals and Johnson & Johnson.

When results of this trial were first released this past August, however, industry analysts said the need for an additional anemia drug on top of the three-drug regimen would greatly discourage use of boceprevir. (See Reuters Health story of Aug 4, 2010.)

Early response was an important predictor of outcome, Dr. Bacon said. The highest SVR, 80%, was seen in patients who had a 1 log decline or greater after four weeks of standard therapy and then received 44 weeks of boceprevir.

"It's a pretty robust improvement in response," the researcher said, adding that the new drug should help a substantial number of patients.

"Some estimates have as many as 300,000 non-responders waiting for treatment," he said.

Attendees at the meeting also heard results of boceprevir treatment in the HCV SPRINT-2 trial, involving 1,097 treatment-na�ve adults in two separate cohorts, one with 938 non-African-American/non-Blacks and the other with 159 African-American/Blacks.

In these patients, boceprevir brought SVR rates up significantly, from 38% in the control group to 63% in the response-guided therapy arm and to 66% in the 48-week treatment arm.