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Telaprevir: Phase 3 ADVANCE Study Data Presented at AASLD
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AASLD: Telaprevir+pEg/RBV Based Combination Therapy in People with Hepatitis C, Regardless of Race or Stage of Liver Disease - 'up to 88% in African-Americans' - (11/01/10) press release
AASLD: New HCV Drugs at AASLD, easy to understand report: (see links below to reports from AASLD) - (11/10/10)
AASLD: Clinical Virology Results from Telaprevir Phase 3 Study ADVANCE - (11/05/10)
AASLD: Telaprevir in Combination with Peginterferon alfa-2a and Ribavirin in Genotype 1 HCV Treatment-Naïve patients: Final results of Phase 3 ADVANCE Study - (11/04/10)
AASLD: Telaprevir Phase 3 ILLUMINATE Study - Final Results Reported at AASLD Nov 2 2010 - (11/04/10)
[Cork, Ireland, 2 Nov 2010] [http://www.pharmiweb.com] - Tibotec BVBA (part of Janssen Pharmaceutical companies of Johnson & Johnson) today announced that a significantly greater proportion of previously untreated patients with chronic genotype 1 hepatitis C virus (HCV) achieved a sustained viral response (SVR) with both 12-week and 8-week telaprevir-based combination regimens (75 percent and 69 percent, respectively), compared to patients treated for 48 weeks with pegylated-interferon and ribavirin alone (44 percent). SVR, which means the virus remains undetectable in patients' blood six months after completion of treatment, is the goal of HCV treatment and is considered a cure. Telaprevir is an investigational DAA (Direct Acting Antiviral) being co-developed by Tibotec and Vertex Pharmaceuticals. Data from the Phase 3 ADVANCE trial will be presented at the 61st annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston.
Professor Geoffrey Dusheiko, from the Centre for Hepatology at the Royal Free Hospital London said, "As a UK clinician, I welcome these groundbreaking new data on telaprevir. The ADVANCE trial shows that 75 percent of patients achieved SVR after receiving 12 weeks of telaprevir combination therapy. Telaprevir in combination with pegylated interferon alpha and ribavirin heralds a significant departure from a decade of pegylated interferon and ribavirin treatment with which only 40-50% patients with genotype 1 HCV achieved SVR, typically after a year of treatment."
In the study, patients were randomized to receive either: telaprevir in combination with pegylated-interferon and ribavirin for 8 weeks followed by additional weeks of pegylated-interferon and ribavirin (T8PR); telaprevir plus pegylated-interferon and ribavirin for 12 weeks followed by additional weeks of pegylated-interferon and ribavirin (T12PR); or pegylated-interferon and ribavirin alone, the current standard of care, for 48 weeks (PR48).1 The rate of achieving SVR, the study's primary efficacy endpoint, was 75 percent (p<0.0001) in the T12PR group (N=363); 69 percent (p<0.0001) in the T8PR group (N=364); and 44 percent is the PR48 group (N=361).1
Patients in the telaprevir-based treatment arms who achieved undetectable rates of HCV RNA at Week 4 (known as rapid viral response, or RVR) and Week 12 of treatment were eligible to receive 24 total weeks of therapy as part of the response-guided design of the study.1 Those who did not meet the criteria but were undetectable at Week 24 received 48 total weeks of therapy. The response-guided approach shortens treatment duration and optimizes the potential for SVR.
For patients in the T12PR group, the T8PR group, and the PR48 group, 68 percent, 66 percent and 9 percent, respectively had undetectable HCV RNA four weeks after the initiation of treatment, defined as a rapid viral response (RVR) by the AASLD Practice Guidelines.1
The safety and tolerability profile of telaprevir was consistent with the profile reported in previous Phase 2 studies. Discontinuation of treatment due to adverse events occurred in 8 percent of the T8PR group, 7 percent of the T12PR group and 4 percent of the PR48 group. Discontinuation of treatment due to rash occurred in 0.5 percent of the T8PR group, 1.4 percent of the T12PR group and 0.0 percent of the PR48 group; due to anemia occurred in 3.3 percent, 0.8 percent and 0.6 percent, respectively.1 The most common adverse events in the telaprevir-based treatment groups were fatigue, pruritus, nausea, headache, anemia, rash, influenza-like illness, insomnia, fever and diarrhea.1 The majority of these adverse events were mild to moderate.
Based on findings from the telaprevir Phase 3 program, Tibotec expects to submit a marketing authorization for telaprevir to the European Medicines Agency (EMEA) in the coming months.
"Results seen in the ADVANCE trial are an important step forward in the fight against this life-threatening disease, as there is an urgent need for new and more effective treatments," said Maria Beumont, Medical Director, Clinical Development, Tibotec. "The current standard of care cures fewer than half of people with genotype 1 HCV, and very limited success is seen in those who are re-treated with the standard of care., As part of our commitment to improving care for people living with hepatitis C, we are also investigating telaprevir in patients who have failed prior treatment."
About the ADVANCE Trial1
ADVANCE was a three-arm, double-blind, randomized, placebo-controlled Phase 3 study that enrolled 1,088 previously untreated people infected with genotype 1 chronic HCV, the most common form of the virus in the U.S. The primary endpoint of the ADVANCE trial was SVR, defined as the proportion of patients who had undetectable HCV RNA both at the end of treatment and 24 weeks after the end of treatment.
Patients in the telaprevir-based treatment groups who achieved RVR or were undetectable at week 12 were eligible to receive 24 total weeks of therapy, while those who did not achieve an extended rapid viral response received a total of 48 weeks of therapy.
Patients received 750 mg of telaprevir (or placebo) orally (tablets) every eight hours (q8h), a 180 mg injection of peginterferon alfa-2a once-weekly, and a 1,000 mg or 1,200 mg weight-based daily oral dose of ribavirin. After 8 weeks of the telaprevir-based regimen, patients in the T8PR group received 16 or 40 weeks of only pegylated-interferon and ribavirin based on response to treatment at week 4 and 12. After 12 weeks of the telaprevir-based regimen, patients in the T12PR group received 12 or 36 weeks of only pegylated-interferon and ribavirin based on response to treatment at week 4 and week 12.
About the Telaprevir Development Program
ADVANCE is the first of three clinical trials conducted as part of a global Phase 3 registration program for telaprevir in treatment-naïve and treatment-failure patients with chronic HCV infection. Data from the ILLUMINATE trial were presented yesterday at the American Association for the Study of Liver Diseases annual meeting. ILLUMINATE evaluated telaprevir-based regimens in approximately 500 treatment-naïve HCV patients. Data from the REALIZE trial will likely be published in 2011. REALIZE is evaluating telaprevir-based regimens in approximately 650 treatment-failure HCV patients.
Telaprevir is being developed by Tibotec in collaboration with Vertex
Pharmaceuticals and Mitsubishi Tanabe Pharma for the treatment of genotype 1 HCV in both patients who have failed prior treatment and in patients who have never been treated. Tibotec has the right to commercialize telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand; Vertex will commercialize telaprevir in the U.S., Canada and Mexico; Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.
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