— CONCISE study will evaluate twice-daily INCIVEK in combination with pegylated-interferon and ribavirin among patients new to treatment and prior relapsers who have the ‘CC' variation near the IL28B gene —
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the initiation of a Phase 3b study called CONCISE that will evaluate the potential for treatment with INCIVEK™ (telaprevir) combination therapy to be shortened to 12 weeks in people with genotype 1 chronic hepatitis C who have the ‘CC' variation near the IL28B gene. INCIVEK (in-SEE-veck) is administered in combination with pegylated-interferon and ribavirin. Approximately one-third of people with hepatitis C have the ‘CC' genotype, which has been associated with higher sustained viral response (SVR, or viral cure) rates and faster response to interferon-based treatment. In this study, INCIVEK will be taken twice a day. The study is expected to enroll 350 people in the United States and Europe who are new to treatment or who have relapsed after at least one prior course of treatment with pegylated-interferon and ribavirin alone. The primary endpoint of the study is the proportion of patients who achieve a sustained viral response 12 weeks after the last planned dose of study drug (SVR12).

"INCIVEK combination therapy is a significant advance over the previous standard of care for the treatment of hepatitis C," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer for Vertex. "As we enter a new era of treatment for hepatitis C, one of our goals is to offer patients a high chance for a cure in the shortest amount of time. This study is one of several ways Vertex is exploring the potential for people with hepatitis C to achieve high viral cure rates with just 12 weeks of total treatment."

A specific genetic region near the IL28B gene is referred to as an IL28B genotype. The three variations of IL28B genotypes (CC, CT or TT) have been correlated with a person's response to hepatitis C treatment with pegylated-interferon and ribavirin.

CONCISE will evaluate the potential to reduce treatment time with INCIVEK combination therapy to 12 weeks and no more than 24 weeks for people with hepatitis C who have the CC variation near the IL28B gene and who have undetectable hepatitis C virus at week 4 of treatment (RVR). This study design is supported by data from studies that have shown that people with hepatitis C who have the CC genotype have better and faster responses to treatment, including retrospective analyses for a group of people who were tested for IL28B genotype in the ADVANCE and REALIZE pivotal studies of INCIVEK. These analyses showed that people in these studies who received INCIVEK combination therapy had substantial improvements in viral cure rates across all IL28B genotypes compared to those treated with pegylated-interferon and ribavirin alone. The highest rates of RVR, extended rapid viral response (eRVR, measured at weeks 4 and 12) and viral cure were observed among people with the CC genotype. Complete results from these analyses were presented in March 2011 at The International Liver Congress™, the 46th annual meeting of the European Association for the Study of the Liver (EASL).

The Phase 3 ADVANCE study evaluated people with hepatitis C who were new to treatment. In this study, 90 percent (45/50) of people with the CC genotype who received INCIVEK combination therapy achieved a viral cure. Seventy-eight percent (39/50) of them achieved an eRVR and were therefore eligible to stop all treatment at 24 weeks. These results were compared to 64 percent (35/55) of patients with the CC genotype who achieved a viral cure with pegylated-interferon and ribavirin alone for 48 weeks.

The Phase 3 REALIZE study evaluated people with hepatitis C who did not achieve a viral cure after at least one prior course of treatment (relapsers, partial responders and null responders). In this study, 88 percent (51/58) of prior relapsers who had the CC genotype and received INCIVEK combination therapy, achieved a viral cure compared to 33 percent (4/12) who were treated with pegylated-interferon and ribavirin alone.

About CONCISE

CONCISE (ChrONiC HepatitIS C and IL28B CC GenotypE) is a randomized, placebo-controlled, global, multi-center Phase 3b study designed to evaluate the efficacy of a 12-week regimen of INCIVEK™ (telaprevir) tablets in combination with pegylated-interferon and ribavirin in approximately 350 people with genotype 1 chronic hepatitis C who have the CC variation at the IL28B gene. In this study, INCIVEK will be dosed as three 375mg tablets twice daily. The study will evaluate people with hepatitis C who are new to treatment as well as those who relapsed after at least one prior course of treatment with pegylated-interferon and ribavirin alone. The primary endpoint of the study is the proportion of patients who achieve a sustained viral response 12 weeks after the last planned dose of study drug (SVR12). All patients will receive INCIVEK in combination with pegylated-interferon and ribavirin for the first 12 weeks of treatment. After the first 12 weeks, patients who achieve a rapid viral response to treatment (measured as undetectable HCV RNA at week 4) will be randomized 2:1 to receive no further treatment or an additional 12 weeks of pegylated-interferon and ribavirin alone. Patients who do not achieve a rapid viral response will receive an additional 36 weeks of treatment with pegylated-interferon and ribavirin alone.

About INCIVEK

INCIVEK is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. INCIVEK was approved by the U.S. Food and Drug Administration (FDA) in May 2011 and by Health Canada in August 2011 for people with genotype 1 chronic hepatitis C with compensated liver disease (some level of damage to the liver but the liver still functions), including cirrhosis (scarring of the liver). INCIVEK is approved for people who are new to treatment, and for people who were treated previously but who did not achieve a sustained viral response or viral cure (relapsers, partial responders and null responders).

INCIVEK (750 mg) is given as two 375 mg tablets three times daily for 12 weeks in combination with pegylated-interferon and ribavirin. Each monthly package of INCIVEK contains four weekly boxes that include daily blister strips. After the first 12 weeks, all patients stop receiving INCIVEK and continue treatment with pegylated-interferon and ribavirin alone for an additional 12 weeks or 36 weeks of treatment. With INCIVEK combination therapy, more than 60 percent of people treated for the first time, as well as those who relapsed after previous therapy, are expected to complete all treatment in 24 weeks. All other patients receive a total of 48 weeks of treatment.

Rash and anemia are the most serious side effects associated with INCIVEK, which led to treatment discontinuation in about 1 percent of people in clinical studies. The most common side effects reported with INCIVEK combination treatment include fatigue, itching, nausea, diarrhea, vomiting, anal or rectal problems, and taste changes.

Vertex developed telaprevir in collaboration with Tibotec BVBA and Mitsubishi Tanabe Pharma. Vertex has rights to commercialize telaprevir in North America where it is being marketed under the brand name INCIVEK (in-SEE-veck). Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In September 2011, telaprevir was approved in the European Union and Switzerland. Telaprevir is known as INCIVO® in Europe. Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries. In September 2011, telaprevir was approved in Japan and will be known as Telavic®.