Tuesday, November 2, 2010

AASLD:Hepatitis C Drug Boceprevir Six Months of Novel Agent Works

AASLD: Six Months of Novel Agent Works in Hep C
By Kristina Fiore , Staff Writer, MedPage Today
Published: November 02, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine

BOSTON -- A shorter, six-month course of the investigational protease inhibitor boceprevir added to standard combination treatment appears just as effective as almost a full year of therapy for patients with a challenging subtype of hepatitis C, researchers reported here.
Sustained virologic response (SVR) rates were similar with both regimens -- 67% for the short course, 68% for the full treatment -- and were both significantly greater than those seen with peginterferon and ribavirin alone (40%, P<0.0001), according to Fred Poordad, MD, of Cedars-Sinai Medical Center in Los Angeles, and colleagues.
They reported their findings during a late-breaking oral session at the American Association for the Study of Liver Diseases meeting here.
Patients with genotype 1 hepatitis C virus have had meager treatment response rates compared with genotype 2 and 3 patients -- especially if they're African American.
So to compare the safety and efficacy of the two strategies in this genotype, as well as outcomes for blacks with this subtype, the researchers enrolled 1,097 treatment-naive patients, 159 of whom were African American, in the SPRINT-2 trial.
Patients were randomized to one of three groups: 48 weeks of interferon and ribavirin along with placebo, 48 weeks of the standard combination plus boceprevir, or 24 weeks of triple therapy.
All three arms had a four-week lead-in phase with peginterferon and ribavirin alone. After that, the two drug groups received an additional 800 mg of boceprevir three times a day.
The primary endpoint was sustained virologic response 24 weeks after therapy.
The researchers found that both boceprevir groups had higher SVR rates at that point than the control group.
In an intention-to-treat analysis among white patients, 67% of those in the short-course group achieved sustained viral response, as did 68% of the long-treatment-course group, compared with just 40% of controls (P<0.0001).
Only 8% of those on full treatment and 9% of those on the short course relapsed, compared with 23% of those on placebo.
Among black patients, 53% of those on the full treatment and 42% of those on the short course had sustained virologic response, compared with 23% of those on placebo (P=0.004 and P=0.044, respectively).
With full treatment, 17% of blacks relapsed, along with 12% of those on the short course and 14% of those on placebo.
The trial had a "stopping rule" mandating that patients discontinue treatment if they don't respond in the first 24 weeks. Among white patients, 27% of those on standard combination therapy discontinued compared with 8% of those on short therapy and 9% of those on the full course.
For blacks, 46% of those on placebo discontinued treatment, compared with 17% of those on the short course and 15% of those on the full course of triple therapy.
Treatment appeared to be associated with two side effects compared with placebo -- anemia and a distorted sense of taste, or disgeusia.
Overall, patients on treatment had greater use of erythropoietin to treat anemia compared with controls (43% for short- and full-course, versus 24% of those on placebo).
More boceprevir patients also had to reduce their treatment dose due to anemia (20% and 21% versus 13%).
Other adverse events included nausea, headache, and fatigue, at similar rates across all three groups.
In a separate trial reported here -- the RESPOND-2 trial -- genotype 1 patients who'd failed prior therapy had better sustained virologic response rates with both the short- and long-course of boceprevir treatment compared with placebo (59% and 67% versus 21%, P<0.0001).
Anemia also appeared to be problematic for the treatment groups in the 403-patient study.
Douglas LaBrecque, MD, of the University of Iowa, who moderated the session at which the SPRINT data were presented, told MedPage Today that the findings are preliminary, but they're still "the best we've seen to date for type 1 patients," especially with regard to results for African-American patients and previous nonresponders.
"It's another step forward, but we're not there yet," he said, adding that triple therapy is still necessary and the standard interferon-ribavirin regimen won't be going away any time soon.
Triple therapy appears to keep resistance issues at bay -- a key area of concern for protease inhibitors, LaBrecque said.
"That's going to be the Achilles' heel of all small-molecule [therapy] trying to get away from [interferon and ribavirin]," he said. "If they start producing significant numbers of resistant virus, then you're developing a much more resistant virus and we don't want to see that."
Drugmaker Merck began submission of a new drug application for boceprevir on a rolling basis and expects to complete that process by the end of the year.
The study was supported by Merck.
Poordad reported relationships with Schering-Plough, Merck, Vertex, Genentech, Bristol-Myers Squibb, Gilead, Pfizer, Salix, Idenix, Valcant, Tibotec, and Abbott.
LaBrecque said he had no disclosures.
Primary source: American Association for the Study of Liver DiseasesSource reference:Poordad F, et al "Boceprevir combined with peginterferon alfa-2b/ribavirin for treatment-naive patients with hepatitis C virus genotype 1: SPRINT-2 final results" AASLD 2010; Abstract LB-4.

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