Phase 3 REALIZE study shows milestone in treatment development for hepatitis C

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that 65% of people overall achieved a sustained viral response (SVR or viral cure) with a telaprevir-based regimen in the pivotal Phase 3 REALIZE study, as compared to 17% of people in the control arm who received pegylated-interferon and ribavirin alone. REALIZE enrolled three groups of patients with genotype 1 hepatitis C who had undergone at least one prior treatment course with pegylated-interferon and ribavirin but did not achieve SVR: (1) those who relapsed, (2) those who achieved a partial response and (3) those who had almost no response, known as a null response. REALIZE is the only Phase 3 hepatitis C study to date of an investigational direct-acting antiviral therapy that was designed to evaluate all major subgroups of people whose prior treatment was unsuccessful, including those who had a null response. The safety and tolerability results were consistent with results from the other two Phase 3 studies of telaprevir. The REALIZE study was conducted by Vertex's collaborator, Tibotec.

“These results may provide hope to people who have not been cured and who are in need of new treatment options, including those with advanced liver disease.”

"The REALIZE data represent a major milestone in the development of new treatments for hepatitis C, as patients who received telaprevir-based therapy had a viral cure rate almost four times greater than the cure rate in those treated with available medicines," said Stefan Zeuzem, M.D., Professor of Medicine and Chief of the Department of Medicine at the JW Goethe University Hospital, Frankfurt, Germany and Principal Investigator of the trial. "These results may provide hope to people who have not been cured and who are in need of new treatment options, including those with advanced liver disease."

"Along with results from ADVANCE and ILLUMINATE, the REALIZE data provide us with a strong understanding of telaprevir's potential role in helping many people with hepatitis C achieve a cure, regardless of their treatment history," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "With these data, we look forward to completing our rolling New Drug Application submission for telaprevir later this year."

Overview of SVR Results

The primary endpoint of the study was SVR in each of the two telaprevir arms compared to the control arm, as well as across the three subgroups of people included in the study. One of the telaprevir treatment arms was designed to evaluate, for the first time, whether there was any further improvement in viral cure rates when delaying the start of telaprevir by four weeks, during which time patients received four weeks of pegylated-interferon and ribavirin alone, compared to a simultaneous start. The SVR rates between these two arms were similar and there was no clinical benefit to the telaprevir delayed start treatment arm in any of the subgroups of patients. The table below combines the two telaprevir arms compared to the control.

SVR rates for the telaprevir simultaneous start arm and the delayed start arm were 64% and 66%, respectively, overall, based on an intent-to-treat (ITT) analysis. For the primary analysis, the SVR rates for the telaprevir simultaneous start arm, delayed start arm and control arm, respectively, were 83%, 88% and 24% in relapsers (p<0.0001); 59%, 54% and 15% in partial responders, (p<0.0001); and 29%, 33% and 5% in null responders, (p<0.001).

Safety & Tolerability Results

The safety and tolerability results of the telaprevir-based regimens in the REALIZE study were consistent with results reported from the Phase 3 ADVANCE and ILLUMINATE studies. The most common adverse events, reported in any treatment arm during the telaprevir dosing periods and up to week 16 to account for the telaprevir delayed start arm in order of frequency, were fatigue, pruritis, headache, rash, flu-like symptoms, nausea and anemia, with the majority being mild to moderate. Of these, fatigue, pruritis, rash, flu-like symptoms, nausea and anemia were more common in the telaprevir-based treatment arms compared to control. Adverse events leading to discontinuation of all study drugs during the telaprevir dosing period and up to week 16 occurred in 4% of people in the combined telaprevir arms and 3% in the control arm during the same period. Discontinuation of all drugs due to anemia and rash during the telaprevir dosing period and up to week 16 occurred in 0.6% and 0.4% of patients, respectively, in the combined telaprevir arms, while discontinuation of all three drugs due to rash and anemia did not occur in the control arm during the same period. As in ADVANCE and ILLUMINATE, the use of erythropoiesis-stimulating agents (ESAs) was not allowed in this study.

Telaprevir is an investigational, oral inhibitor of HCV protease, an enzyme essential for viral replication, and is being developed by Vertex Pharmaceuticals in collaboration with Tibotec Pharmaceuticals and Mitsubishi Tanabe Pharma. With results from the three Phase 3 studies of telaprevir - ADVANCE, ILLUMINATE and REALIZE - Vertex is on track to complete its rolling New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) in the fourth quarter of 2010.

Patient Demographics

REALIZE enrolled people with hepatitis C who did not achieve a viral cure after receiving at least one course of prior treatment with pegylated-interferon and ribavirin. Patients in the study were enrolled based on their response to prior treatment: 53% were prior relapsers, 19% were prior partial responders and 28% were prior null responders. In this study, 26% of patients overall had cirrhosis and 89% of patients overall had a high viral load (HCV RNA ≥ 800,000 IU/mL) when entering the study. Specifically in the null responder population, there were an even greater number of people with cirrhosis (33%) and high viral load (95%). Approximately 50% of patients were genotype 1a and 50% were genotype 1b.

Source:  Vertex Pharmaceuticals