Telaprevir Improved Outcomes for Hep C Patients Who Failed Prior Therapy

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 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 of Inova Fairfax Hospital in Falls Church, Va. "Re-treating 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 in a press conference at the annual Digestive Disease Week.

The researchers, led by Dr. Paul Pockros of the Scripps Translational Science Institute in La Jolla, Calif., conducted an 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 a 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.

Approximately 70% of the 662 treated patients were male, and 93% were white. About one-quarter (26%) had cirrhosis, and 89% had a baseline HCV RNA level of at least 800,000 IU/mL. They 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 noted.

The safety and tolerability data for telaprevir were similar to results from previous studies, Dr. Younossi said. 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, he said.

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. At press time, neither drug had been approved, but approval was considered imminent for both drugs.

Dr. Younossi has served on advisory committees or review boards for multiple pharmaceutical companies, including study sponsor Vertex Pharmaceuticals.

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 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 of Inova Fairfax Hospital in Falls Church, Va. "Re-treating 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 in a press conference at the annual Digestive Disease Week.

The researchers, led by Dr. Paul Pockros of the Scripps Translational Science Institute in La Jolla, Calif., conducted an 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 a 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.

Approximately 70% of the 662 treated patients were male, and 93% were white. About one-quarter (26%) had cirrhosis, and 89% had a baseline HCV RNA level of at least 800,000 IU/mL. They 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 noted.

The safety and tolerability data for telaprevir were similar to results from previous studies, Dr. Younossi said. 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, he said.

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. At press time, neither drug had been approved, but approval was considered imminent for both drugs.

Dr. Younossi has served on advisory committees or review boards for multiple pharmaceutical companies, including study sponsor Vertex Pharmaceuticals.

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 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 of Inova Fairfax Hospital in Falls Church, Va. "Re-treating 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 in a press conference at the annual Digestive Disease Week.

The researchers, led by Dr. Paul Pockros of the Scripps Translational Science Institute in La Jolla, Calif., conducted an 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 a 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.

Approximately 70% of the 662 treated patients were male, and 93% were white. About one-quarter (26%) had cirrhosis, and 89% had a baseline HCV RNA level of at least 800,000 IU/mL. They 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 noted.

The safety and tolerability data for telaprevir were similar to results from previous studies, Dr. Younossi said. 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, he said.

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. At press time, neither drug had been approved, but approval was considered imminent for both drugs.

Dr. Younossi has served on advisory committees or review boards for multiple pharmaceutical companies, including study sponsor Vertex Pharmaceuticals.