Data from two Phase 3 telaprevir clinical trials for chronic genotype 1 hepatitis C (HCV), ADVANCE and REALIZE, has been published in the New England Journal of Medicine. The studies show that treatment with telaprevir, an investigational direct-acting antiviral (DAA), combined with pegylated-interferon and ribavirin (PR) significantly improved cure rates (known as sustained virologic response or SVR) compared to PR alone for both previously untreated patients and patients who have failed previous treatment, including those demonstrating no response to previous therapy (null responders) The REALIZE results further show significant improvement in cure rates for all types of previously treated patients regardless of whether there was a 4 week lead-in to treatment with PR.

"There are currently more than 170 million people worldwide chronically infected with HCV, however the current standard of treatment, pegylated-interferon combined with ribavirin, cures less than half of patients infected with genotype 1, starting therapy for the first time. The publication of results of ADVANCE and REALIZE in the New England Journal of Medicine demonstrates the benefits of telaprevir therapy for these patients. The REALIZE results also demonstrate the first time a compound with this new mode of action has shown efficacy in all types of previously treated patients including null responders in a Phase 3 study." said Stefan Zeuzem, lead investigator of the REALIZE trial and Chief of the Department of Medicine, Johann Wolfgang Goethe University Hospital, Frankfurt, Germany.

Results from the ADVANCE trial showed that a significantly greater proportion of previously untreated patients with chronic genotype 1 HCV achieved SVR (75 percent 12 week regimen and 69 percent 8 week regimen), compared to patients treated with PR alone (44 percent, p<0.001). Patients whose HCV ribonucleic acid (RNA) was undetectable at week 4 or 12 (58% of total study population) were assigned to a 24 week treatment duration consisting of 8- or 12-weeks of telaprevir-based combination regimens followed by 12 weeks of PR alone. SVR rates for this group were 83 percent for the 8-week telaprevir arm and 89 per cent for the 12-week telaprevir arm.

Results from the REALIZE trial showed that a significantly greater proportion of patients who failed previous treatment achieved SVR with a telaprevir-based regimen compared to patients who received PR alone. REALIZE enrolled three groups of patients with genotype 1 HCV who had undergone at least one prior treatment course with PR but did not achieve cure: (1) those who relapsed, (2) those who achieved a partial response and (3) null responders. For these groups, SVR rates were 83 percent (p<0.001) for relapsers and 41 percent (p<0.001) for non-responders in the T12/PR48 group (N=266), 88 percent (p<0.001) for relapsers and 41 percent (p<0.001) for non-responders in the Lead-inT12/PR48 group (N=264) and 24 percent for relapsers and 9 percent for non-responders in the PR48 group (N=132).

In both the ADVANCE and REALIZE studies, telaprevir was evaluated in combination with PR compared to 48 weeks of PR alone. The most common adverse events reported in patients receiving telaprevir were anemia, skin events (rash, pruritus), fatigue, nausea and headache and were consistent with previous studies.

These data along with those from the ILLUMINATE study, presented at the 61st Annual Meeting of the American Association for the Study of Liver Diseases, 2010, formed the basis of a Marketing Authorisation Application for telaprevir, submitted to the European Medicines Agency (EMA) for the treatment of chronic genotype 1 HCV, which was accepted for accelerated assessment. Telaprevir was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and will be marketed by Vertex Pharmaceuticals under the brand name INCIVEKTM. Following marketing authorization approvals, telaprevir will be marketed in the EU and other territories under the brand name INCIVO® by Janssen companies.

About the ADVANCE Study

ADVANCE was a three-arm, double-blind, randomized, placebo-controlled Phase 3 study that enrolled 1,088 previously untreated people infected with chronic genotype 1 HCV, the most common form of the virus in Europe. 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 undetectable viral loads at weeks 4 and 12 (eRVR) were eligible to receive a total of 24 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 µg injection of peginterferon alfa-2a once-weekly, and a 1,000 mg or 1,200 mg weight-based daily oral dose of ribavirin. After 12 weeks of the telaprevir-based regimen, patients in the T12PR group received 12 or 36 weeks of only PR. This was based on their response to treatment at week 4 and week 12.

About the REALIZE Study

REALIZE was a randomized, double-blind, placebo-controlled Phase 3 trial to compare the efficacy, safety and tolerability of telaprevir in 662 patients with chronic genotype 1 HCV. who failed prior treatment with PR. The primary objective was to evaluate the superior efficacy of the telaprevir arms for non-responders (null and partial responders) and relapsers.

The secondary objectives included the evaluation of a delayed start to treatment (known as lead-in) with PR arm and efficacy in prior null- and partial-responders separately.

In both telaprevir regimens (T12/PR48 and Lead-in T12/PR48), patients received 12 weeks of 750 mg of telaprevir every eight hours, as well as 48 weeks of PR. Telaprevir was given orally (tablets) at a dose of 750 mg every eight hours for 12 weeks. Pegylated-interferon was given as an injection under the skin at a dose of 180 µg once every week for 48 weeks. Ribavirin was given orally at a dose of either 1000 or 1200 mg (depending on body weight) two times per day for 48 weeks.

The rate of achieving SVR for prior relapsers and non-responders, the study's primary efficacy endpoint, was 83 percent (p<0.001) for relapsers and 41 percent (p<0.001) for non-responders in the T12/PR48 group (N=266), 88 percent (p<0.001) for relapsers and 41 percent (p<0.001) for non-responders in the Lead-inT12/PR48 group (N=264) and 24 percent for relapsers and 9 percent for non-responders in the PR48 group (N=132). Data also show that 59 percent (p<0.001) of partial responders and 29 percent (p<0.001) of null-responders achieved SVR.

About Telaprevir

Telaprevir is being developed by Tibotec, one of the Janssen Pharmaceutical Companies of Johnson & Johnson, in collaboration with Vertex Pharmaceuticals and Mitsubishi Tanabe Pharma. Janssen has the right to commercialize telaprevir in Europe, Latin America, the Middle East, Africa, India, Australia and New Zealand under the commercial name INCIVO®; Vertex will commercialize telaprevir in the N.America under the name INCIVEK™; Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

On May 23rd 2011, US FDA approved telaprevir for the treatment of people with chronic genotype 1 hepatitis C with compensated liver disease.

About HCV

HCV is a blood-borne infectious disease that affects the liver. With an estimated 170 million people infected worldwide, and three to four million people newly infected each year, HCV puts a significant burden on patients and society. Chronic infection with HCV can lead to liver cancer and other serious and fatal liver diseases, and is the most common cause of liver transplant in Europe. The current standard of care for HCV, pegylated-interferon combined with ribavirin, may be associated with serious side effects in some patients and only cures 40-50 percent of genotype 1 patients.

Source: Tibotec