By Alan Franciscus, Editor-in-Chief HCVAdvocate
Vertex Announces Phase III Studies
On January 23, 2008, Vertex announced that they are moving forward on clinical studies of telaprevir in combination with Pegasys (pegylated interferon-2a) and ribavirin in the United States, Europe and other unspecified countries.
Primary Pivotal Study
The primary study is expected to begin recruitment of more than 1050 HCV patients in March 2008. The study will recruit HCV treatment-naive (never been treated) genotype 1 patients from over 100 centers in the U.S., Europe and other countries. The trial participants will be randomized into three treatment arms:
• Arm 1: telaprevir dosed at 750 mg every eight hours for 12 weeks in combination with standard doses of Pegasys and ribavirin, then an additional treatment period of 12 weeks of standard doses of Pegasys plus ribavirin alone (without telaprevir). (Total: 24 week treatment duration)
• Arm 2: telaprevir dosed at 750 mg every eight hours for 8 weeks in combination with standard doses of Pegasys and ribavirin, with an additional treatment period of 16 weeks with standard doses of Pegasys plus ribavirin alone. (Total: 24 week treatment duration)
• Arm 3: Control arm of standard doses of Pegasys plus ribavirin. (Total: 48 week treatment duration)
A key component of the study will be rapid virological response (RVR) – the patients in the telaprevir arms who achieve an RVR (HCV RNA less than 10 IU/mL) at week 4, and who are still undetectable at week 12 will receive a total of 24 weeks of treatment. The patients in the telaprevir arms who do not achieve an RVR, but who are undetectable at week 24 will continue on standard doses of Pegasys plus ribavirin for a total treatment period of 48 weeks.
Second Study
An additional study is being planned with telaprevir in combination with pegylated interferon plus ribavirin therapy that will be conducted simultaneously with the above study to gather more information on the effectiveness of telaprevir/pegylated interferon/ribavirin therapy to compare the 48-week treatment period to the 24-week treatment period in HCV genotype 1 treatment-naïve patients. The main reason for this study is to further validate the 24 week treatment period to make sure it is as effective as the current standard 48-week treatment period.
The primary end point of the telaprevir clinical trials is sustained virological response (SVR), which means that HCV RNA is undetectable (less than 10 IU/mL) 24 weeks after the completion of therapy.
Additional Studies
Vertex and its partner Tibotec are also conducting many additional clinical trials in the U.S. and Europe. The one that is the most eagerly awaited is the Prove 3 clinical trial that is studying the use of telaprevir in combination with pegylated interferon plus ribavirin in HCV genotype 1 patients who have not achieved an SVR with a previous course of pegylated interferon-based therapy. The results of this study are expected around mid-2008.
Another study that Tibotec is conducting uses a different dosing schedule of telaprevir (every 8 hours vs. every 12 hours) in combination with pegylated interferon plus ribavirin. Interim 12 week data is expected mid-2008. Tibotec is also conducting studies on people with genotypes 2 and 3, and in December 2007 Tibotec began a Phase II study on people infected with HCV genotype 4.
Bottom Line
The results from the Phase III pivotal study of telaprevir in combination with pegylated interferon plus ribavirin therapy in HCV genotype 1 treatment-naïve patients along with the results of the Phase II treatment duration study (48 weeks vs. 24 weeks) will be submitted to the FDA for marketing approval. Vertex has stated that the clinical trial data should be available in mid-2010 and that they expect to file an application to the Food and Drug Administration for marketing approval of the combination of telaprevir, pegylated interferon and ribavirin by the end of 2010.
This is encouraging news because the combination of telaprevir, pegylated interferon plus ribavirin might be approved for the treatment of genotype 1 treatment-naïve patients by the FDA and available to the general hepatitis C population by mid-to-end 2011.
Albuferon Dosing Adjusted
Albuferon in combination with ribavirin is currently in Phase III clinical studies. In January 2008 Human Genome Sciences announced that, based on the recommendations of an independent Data Monitoring Committee (DMC), the arm in which the patients were receiving the highest dose (1200-mcg dose) will be closed out and that the people in the 1200-mcg dose arm will be moved over to the 900-mcg dose arm group. The reason the 1200-mcg dose arm is being discontinued is due to safety concerns regarding pulmonary (lung) adverse events. In a company press release, Human Genome Sciences (HGS) stated that the closing of the 1200-mcg dosing arm will not affect the scheduled completion of the study and subsequent filing to the FDA for marketing approval, which is expected in late 2009. It was also stated in the HGS press release that the DMC did not express any safety concerns about the 900-mcg dose of Albuferon.
Albuferon is a form of long-acting interferon that is being tested to find out if an injection of Albuferon once every two weeks is as effective as the once weekly dose of pegylated interferon alfa-2a (Pegasys). Both drugs are being given in combination with ribavirin. Originally HGS was testing Albuferon as a once every 4 week injection, but there hasn’t been any data that would support further development of this therapeutic approach.
