BY HEIDI SPLETE
Elsevier Global Medical News
CHICAGO – Adding the protease inhibitor telaprevir to the standard combination therapy of pegylated interferon alfa-2a and ribavirin significantly improved outcomes in three categories of
genotype 1 hepatitis C patients who had previously failed standard treatment, according to final results from the phase III REALIZE trial.
Approximately 60% of genotype 1 hepatitis C patients treated with standard
therapy do not respond, said Dr. Zobair M. Younossi, AGAF, of Inova
Fairfax Hospital in Falls Church, VA. “Retreating these patients will be
very difficult if you want to treat them with the currently available
double combination therapy,” said Dr. Younossi, who presented the
study findings during a press conference at the annual Digestive Disease Week.
The researchers, led by Dr. Paul Pockros, AGAF, of the Scripps
Translational Science Institute in La Jolla, Calif., conducted this international, multicenter, double-blind,randomized placebo-controlled trial
– the REALIZE trial – to assess the safety and tolerability of adding
750 mg of telaprevir every 8 hours to the standard therapy of 180 mcg/week
of pegylated interferon alfa-2a and 1000-1200 mg/day of ribavirin. The
control group received the standard therapy plus placebo.
The treatment arms were as follows:
telaprevir plus standard therapy for 12 weeks followed by standard therapy
for 36 weeks; standard therapy for 4 weeks followed by telaprevir plus standard therapy for
12 weeks and then standard therapy for 32 weeks; and standard therapy for 48 weeks.
About 70% of the 662 treated patients were male, and 93% of patients
were white. About one-quarter (26%)had cirrhosis, and 89% had a baseline
HCV RNA level of at least 800,000 IU/mL. The patients were divided into
three groups: those who had relapsed after standard treatment, those who
had a partial response to standard treatment,and those who had no response
to standard treatment.
Among the prior relapsers, the response rate in the telaprevir patients
was 83%-88%, compared with 23% in the placebo group. Among the prior
partial responders, the response rate in the telaprevir patients ranged from 54% to 59%, compared with 23% of the placebo patients. And among the prior nonresponders, the response rate was 29% to 33% in the telaprevir group and 5% in the placebo group. The differences between telaprevir and placebo were significant in all three patient categories
– prior partial responders, prior nonresponders, and prior relapsers.
The main goal of the study was to assess whether telaprevir together with
standard therapy had superior efficacy for prior relapsers and prior nonresponders, compared with standard therapy alone.
“Another important part of the study was that the lead-in phase did not add
to the efficacy and the sustained virologic response in these patients,” Dr. Younossi explained in an interview.
The safety and tolerability data for telaprevir were similar to the results
from previous studies, Dr. Younossi added. In the current study, the most frequently reported adverse events included fatigue, pruritus, rash, nausea, flulike symptoms, anemia, and diarrhea. Rash (4%) and anemia (3%) were the most common reasons given for treatment discontinuation.
“We are on the verge of the next wave of treatment for hepatitis C,” said
the moderator of the press conference,Dr. Adrian M. Di Bisceglie, codirector of the liver center and chief of hepatology, St. Louis University.
Both telaprevir and boceprevir (which was not evaluated in the REALIZE trial)are protease inhibitors; they are direct-acting antivirals that have been tested in phase III trials with pegylated interferon and ribavirin, Dr. Di Bisceglie noted.
On April 27, the Antiviral Drugs Advisory Committee of the U.S. Food and
Drug Administration unanimously voted to recommend approval of boceprevir
and, on April 28, unanimously voted to recommend approval of telaprevir, both for use in combination with pegylated interferon and ribavirin as a treatment for genotype 1 chronic hepatitis C. Both telaprevir and boceprevir subsequently received FDA approval.
Dr. Younossi has served on advisory committees or review boards for multiple pharmaceutical companies, including the study sponsor, Vertex Pharmaceuticals.
■ To view a video about this study and others presented at
DDW 2011, scan this QR code with your smartphone.
Don’t have a QR reader? Get one at
http://www.mobiletag.com/
http://www.gastro.org/journals-publications/gi-hepatology-news/GI_-_Hepatology_News_-_July_2011.pdf
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