Vertex Pharmaceuticals
Oct 24, 2011
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Vertex Starts Global Phase 3b Study to Evaluate the Potential for People with Hepatitis C to Achieve a Viral Cure (SVR) with a Total Treatment Duration of 12 Weeks of INCIVEK™ Combination Therapy

— 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®.

IMPORTANT SAFETY INFORMATION

Indication

INCIVEK™ (telaprevir) is a prescription medicine used with the medicines peginterferon alfa and ribavirin to treat chronic (lasting a long time) hepatitis C genotype 1 infection in adults with stable liver problems, who have not been treated before or who have failed previous treatment. It is not known if INCIVEK is safe and effective in children under 18 years of age.

Important Safety Information

INCIVEK should always be taken in combination with peginterferon alfa and ribavirin. Ribavirin may cause birth defects or death of an unborn baby. Therefore, a patient should not take INCIVEK combination treatment if she is pregnant or may become pregnant, or if he is a man with a sexual partner who is pregnant. Patients must use two forms of effective birth control during treatment and for the 6 months after treatment with these medicines.

INCIVEK and other medicines can affect each other and can also cause side effects that can be serious or life threatening. There are certain medicines patients cannot take with INCIVEK combination treatment. Patients should tell their healthcare providers about all the medicines they take, including prescription and non-prescription medicines, vitamins and herbal supplements.

INCIVEK can cause serious side effects including rash and anemia. The most common side effects of INCIVEK include itching, nausea, diarrhea, vomiting, anal or rectal problems, taste changes and tiredness. There are other possible side effects of INCIVEK, and side effects associated with peginterferon alfa and ribavirin also apply to INCIVEK combination treatment. Patients should tell their healthcare providers about any side effect that bothers them or doesn't go away.

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

INCIVEK™ is a trademark of Vertex Pharmaceuticals Incorporated.

PEGASYS® and COPEGUS® are registered trademarks of Hoffmann-La Roche.

About Hepatitis C

Hepatitis C is a serious liver disease caused by the hepatitis C virus, which is spread through direct contact with the blood of infected people and ultimately affects the liver.1 Chronic hepatitis C can lead to serious and life-threatening liver problems, including liver damage, cirrhosis, liver failure or liver cancer.1 Though many people with hepatitis C may not experience symptoms, others may have symptoms such as fatigue, fever, jaundice and abdominal pain.1

Unlike HIV and hepatitis B virus, chronic hepatitis C can be cured.2 However, approximately 60 percent of people do not achieve SVR,3,4,5 or viral cure,6 after treatment with 48 weeks of pegylated-interferon and ribavirin alone. If treatment is not successful and a person does not achieve a viral cure, they remain at an increased risk for progressive liver disease.7,8

More than 170 million people worldwide are chronically infected with hepatitis C.6 In the United States, nearly 4 million people have chronic hepatitis C and 75 percent of them are unaware of their infection.9 Hepatitis C is four times more prevalent in the United States compared to HIV.9 The majority of people with hepatitis C in the United States were born between 1946 and 1964, accounting for two of every three people with chronic hepatitis C.10 Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 4,600 to 12,000 deaths annually.11,12 By 2029, total annual medical costs in the United States for people with hepatitis C are expected to more than double, from $30 billion in 2009 to approximately $85 billion.9

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including statements regarding (i) 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; (ii) the clinical trial design of the CONCISE study, including the number of patients the company expects to enroll in the clinical trial; and (iii) Vertex's goal to offer patients a high chance for a cure in the shortest amount of time. While the company believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that the outcomes from this clinical trial may not be favorable; that future scientific, clinical, competitive or other market factors may adversely affect the potential for telaprevir-based therapy and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through Vertex's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

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, rheumatoid arthritis, 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. Today, Vertex has more than 1,900 employees around the world, and Science magazine named Vertex number one on its 2011 list of Top Employers in the life sciences.

(VRTX-GEN)

1 Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf. Accessed March 21, 2011.

2 Pearlman BL and Traub N. Sustained Virologic Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection: A Cure and So Much More. Clin Infect Dis. 2011 Apr;52(7):889-900.

3 Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001;358:958-965.

4 Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

5 McHutchison JG, Lawitz EJ, Shiffman ML, et al; IDEAL Study Team. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580-593.

6 Ghany MG, Strader DB, Thomas DL, Seeff, LB. Diagnosis, management and treatment of hepatitis C; An update. Hepatology. 2009;49 (4):1-40.

7 Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008;50(Suppl 4):357A (Abstract 115).

8 Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

9 Institute of Medicine of the National Academies. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM and Mitchell AE, ed. Available at: http://www.iom.edu/Reports/2010/Hepatitis-and-Liver-Cancer-A-National-Strategy-for-Prevention-and-Control-of-Hepatitis-B-and-C.aspx. Updated January 11, 2010. Accessed March 21, 2011.

10 Pyenson B, Fitch K, Iwasaki K. Consequences of hepatitis C virus (HCV): Costs of a baby boomer epidemic of liver disease. Available at: http://www.natap.org/2009/HCV/051809_01.htm. Updated May 2009. Accessed March 21, 2011. This report was commissioned by Vertex Pharmaceuticals, Inc.

11 Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009;50(6):1750-1755.

12 Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW. Aging of hepatitis C virus (HCV)-infected persons in the United States: A multiple cohort model of HCV prevalence and disease progression. Gastroenterology. 2010;138:513-521.

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