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4-Drug Regimen Can Cure Genotype 1 Hepatitis C in 12 Weeks

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Interim results from the Phase 2 ZENITH study show that previously untreated people with HCV genotype 1 can achieve sustained response in as little as 12 weeks using a quadruple regimen consisting of telaprevir (Incivek), the experimental HCV polymerase inhibitor VX-222, pegylated interferon, and ribavirin. A newly added arm will evaluate telaprevir, VX-222, and ribavirin without interferon.

Below is an edited excerpt fro a Vertex Pharmaceuticals press release describing the study and its findings.

Interim Data from Phase 2 Study of Combination Regimen Including VX-222 and Incivek Suggest Potential to Treat Genotype 1 Hepatitis C in as few as 12 Weeks and No More Than 24 Weeks

First data to show potential for viral cure in many patients with a 12-week combination regimen of multiple direct-acting antivirals

Cambridge, Mass. -- July 26, 2011 -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced interim results from ZENITH, an ongoing Phase 2 study designed to assess the safety, tolerability and efficacy of multiple 12- and 24-week response-guided treatment regimens with VX-222 (400 mg or 100 mg), its lead polymerase inhibitor in development, in combination with Incivek (telaprevir) tablets, pegylated interferon and ribavirin in people with genotype 1 chronic hepatitis C who were new to treatment.

This is an interim analysis from patients in the four-drug treatment arms and was conducted after these patients completed their assigned treatment. Results showed that 50 percent of people (15/30) in the study who received VX-222 (400 mg) in combination with Incivek, pegylated interferon and ribavirin were eligible to stop all treatment at week 12, and 93 percent (14/15) of these patients had undetectable hepatitis C virus 12 weeks after treatment ended (sustained viral response 12, or SVR12). Patients from the VX-222 (400 mg) treatment arm who were not eligible to stop all treatment at week 12 received an additional 12 weeks of pegylated interferon and ribavirin alone for 24 total weeks of treatment. The hepatitis C virus was undetectable in 100 percent (13/13) of these patients at the end of 24 weeks.

In this study, VX-222, Incivek and ribavirin were given twice daily (BID). Interim safety results from the four-drug treatment arms showed that mild gastrointestinal symptoms and mild fatigue were the most frequently reported adverse events. Side effects consistent with the known safety profile of Incivek combination treatment also were observed.

"The results from this study are the first to show the potential for a combination of multiple direct-acting antiviral medicines to help people with hepatitis C clear the virus with as few as 12 and no more than 24 weeks of treatment," said Robert Kauffman, MD, PhD, Senior Vice President and Chief Medical Officer for Vertex. "We look forward to additional data from this study, including data from the ongoing all-oral treatment arms, which will guide our future development plans with the goal of further improving treatment."

ZENITH is an ongoing Phase 2 study that initially enrolled 106 people with genotype 1 chronic hepatitis C and began with four treatment arms designed to evaluate multiple response-guided treatment regimens with VX-222, Vertex's lead polymerase inhibitor in development, in combination with Incivek, Pegasys (pegylated interferon alfa-2a) and Copegus (ribavirin), three medicines approved to treat hepatitis C. In this study, VX-222, Incivek and ribavirin were given twice daily. The primary endpoint of the study is safety and tolerability. The secondary endpoint is on-treatment antiviral activity and the proportion of people in each treatment arm who achieve a sustained viral response. Additional results from this study will be submitted for presentation at an upcoming medical meeting.

Arms A (n=18) and B (n=29) were designed to evaluate all-oral, two-drug combination regimens of VX-222 (400 mg or 100 mg) and Incivek (1,125 mg). Data presented in March at the International Liver Congress 2011, the 46th annual meeting of the European Association for the Study of the Liver (EASL), in Berlin, Germany, showed significant initial antiviral activity in people who were treated with VX-222 (400 mg) and Incivek. However, these treatment arms were discontinued due to a pre-defined stopping rule related to viral breakthrough. Arms C (n=29) and D (n=30) are ongoing and are designed to evaluate four-drug combination regimens of VX-222 (400 mg or 100 mg), Incivek (1,125 mg), pegylated interferon and ribavirin.

Data announced today are from the four-drug treatment arms (Arms C and D). In these two arms, patients were assigned to take all four medicines for the first 12 weeks of treatment. People who had undetectable hepatitis C virus levels in the blood (HCV RNA) at weeks two and eight of treatment were eligible to stop all treatment at week 12. In this study, the amount of hepatitis C virus in the blood was measured by the Roche COBAS Taqman HCV test (<10 IU/mL undetectable). People who did not meet these criteria were assigned to receive 24 total weeks of treatment: 12 weeks of the four-drug combination regimen followed by 12 weeks of pegylated interferon and ribavirin alone. This interim analysis includes SVR12 results for the people who were eligible for and completed 12 total weeks of treatment and end-of-treatment results for the people who were assigned to and completed 24 total weeks of treatment.

ZENITH: Interim Analysis

 

 

SVR12 in people who
were eligible for and
completed 12 total
weeks of treatment

 

Undetectable hepatitis C
virus in people who were
assigned to and
completed 24 weeks of
treatment

 

Undetectable
hepatitis C virus at
week 24 for all
patients (intent-to-
treat analysis)

VX-222 (400 mg), Incivek,
pegylated interferon and ribavirin*
(n=30)

 

93%

(14/15)+

 

100%

(13/13)

 

90%

(27/30)

VX-222 (100 mg), Incivek,
pegylated interferon and ribavirin**
(n=29)

 

82%

(9/11)++

 

93%

(13/14)^

 

83%

(24/29)

SVR12: undetectable hepatitis C virus 12 weeks after treatment ended.

*50 percent (15/30) had undetectable hepatitis C virus at weeks 2 and 8 and were eligible to stop all treatment at week 12. Two people in the VX-222 (400 mg) treatment arm discontinued treatment before week 12 and did not achieve SVR12.

**38 percent (11/29) had undetectable hepatitis C virus at weeks 2 and 8 and were eligible to stop all treatment at week 12. Four people in the VX-222 (100 mg) treatment arm discontinued treatment before week 12 and two of them achieved SVR12.

+One person in the 12-week VX-222 (400 mg) treatment arm relapsed.

++Two people in the 12-week VX-222 (100 mg) treatment arm relapsed.

^24-week end-of-treatment data are not available for one patient.

Two additional treatment arms (E and F) were added to the study to evaluate a three-drug, all-oral, interferon-free regimen of VX-222 (400 mg), Incivek and ribavirin. Enrollment in these treatment arms is expected to be complete by the end of the third quarter of 2011. Arm E will evaluate people with genotype 1b chronic hepatitis C and Arm F will evaluate people with genotype 1a chronic hepatitis C. Vertex expects to report data from the all-oral treatment arms in the first half of 2012.

Interim Safety and Tolerability Results from the Four-drug Treatment Arms

The most frequent adverse events observed in the four-drug treatment arms were fatigue, nausea, diarrhea, anemia, pruritis (itchiness) and rash. The majority of events were mild or moderate. Mild diarrhea occurred more frequently in the VX-222 (400 mg) treatment arm. The majority of people in the study did not use medication to control diarrhea. There were no treatment discontinuations due to diarrhea. Six patients discontinued treatment due to adverse events; three each from the 400 mg and 100 mg treatment arms. Two people from each arm discontinued treatment before week 12 and one person in each arm discontinued treatment between weeks 12 and 24 while they were receiving pegylated interferon and ribavirin alone.

About Incivek and VX-222

Incivek (in-SEE-veck) is an oral medicine that acts directly on the hepatitis C virus protease, an enzyme essential for viral replication. In May 2011, Incivek was approved by the U.S. Food and Drug Administration (FDA) for a broad group of 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 SVR, or viral cure (relapsers, partial responders and null responders).

VX-222 is an oral medicine in development that is a non-nucleoside inhibitor of the HCV NS5B polymerase. VX-222 is currently being evaluated in combination with INCIVEK, pegylated interferon and ribavirin in a Phase 2 study. Vertex has worldwide commercial rights for VX-222.

Vertex developed telaprevir in collaboration with Tibotec Vicro-Virology BVBA, one of the Janssen Pharmaceutical companies of Johnson & Johnson, and Mitsubishi Tanabe Pharma. Vertex is commercializing telaprevir in North America, where it is known as Incivek. Through its affiliate, Janssen, Tibotec has rights to commercialize telaprevir in Europe, South America, Australia, the Middle East and certain other countries. In July 2011, Janssen announced that the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for Incivo (telaprevir). Mitsubishi Tanabe Pharma has rights to commercialize telaprevir in Japan and certain Far East countries.

Please see full Prescribing Information for Incivek, including the Medication Guide, available at www.Incivek.com.

About Vertex

Vertex creates new possibilities in medicine. Our team discovers, develops and commercializes innovative therapies so people with serious diseases can lead better lives.

Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of hepatitis C, cystic fibrosis, epilepsy and other life-threatening diseases.

Founded more than 20 years ago in Cambridge, MA, we now have ongoing worldwide research programs and sites in the U.S., U.K. and Canada.

For more information see www.vrtx.com.

8/2/11

Source

Vertex Pharmaceuticals. Interim Data from Phase 2 Study of Combination Regimen Including VX-222 and Incivek Suggest Potential to Treat Genotype 1 Hepatitis C in as few as 12 Weeks and No More Than 24 Weeks. Press release. July 26, 2011.