December 9, 2011

BusinessWire · Dec. 9, 2011 | Last Updated: Dec. 9, 2011 3:00 AM ET

For media outside of the U.S.A. only

Boehringer Ingelheim today announced that the final patient has been randomised to treatment in the large-scale Phase III clinical trial programme for BI 201335, its investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV).

The extensive study programme is underway at more than 350 sites in 15 countries and together encompasses nearly 2,000 treatment-experienced as well as treatment-naïve patients. Key regions in the programme include the European Union, Japan, U.S., Canada, Taiwan, Korea and Russia.

The programme consists of three Phase III trials, that will be conducted to evaluate BI 201335 plus the standard backbone treatment, pegylated interferon (pegIFN) and ribavirin (RBV) in patients with chronic genotype-1 HCV. Most HCV patients are infected with genotype-1 virus and belong to the most challenging HCV group to treat. The study programme evaluates “sustained viral response” (SVR) as the primary clinical endpoint, which is considered viral cure. Results from the Phase III studies are expected in the first half of 2013.

The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the entire BI 201335 programme. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.

“We are progressing our BI 201335 programme with a high priority to leverage its potential to improve cure rates in HCV treatment,” said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “We believe our HCV-pipeline may become an important tool to fight a chronic disease that affects over 170 million people worldwide.”

Phase IIb results presented last month showed that the interferon-free combination of BI 201335, with Boehringer Ingelheim’s polymerase inhibitor BI 207127 (SOUND-C2), led to 76% of patients achieving a virological response at week 12, with 63% achieving SVR12 (undetectable virus, 12 weeks post-treatment) with 16 weeks treatment. These results were presented at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, USA, alongside SILEN-C1 and SILEN-C3 study results which showed the potential for BI 201335/ PegIFN/RBV to shorten treatment duration and improve the likelihood of viral cure (SVR). These Phase IIb results provide a strong basis for further development as BI 201335 progresses through Phase III.

NOTES TO EDITORS

SOUND-C2

SOUND-C2 is an open-label, randomised, Phase IIb study where 362 treatment-naïve GT1 HCV patients were randomised into five interferon-free treatment groups, each with 120mg BI 201335 once daily but with different dosing of BI 207127 and treatment durations as follows:

  • BI 201335 120mg QD + BI 207127 600mg TID + RBV for 16 weeks;
  • BI 201335 120mg QD + BI 207127 600mg TID + RBV for 28 weeks;
  • BI 201335 120mg QD + BI 207127 600mg TID + RBV for 40 weeks;
  • BI 201335 120mg QD + BI 207127 600mg BID + RBV for 28 weeks; or
  • BI 201335 120mg QD + BI 207127 600mg TID without RBV for 28 weeks.

SILEN-C1

SILEN-C1 is a double-blind, placebo-controlled trial, that randomised 429 treatment-naïve GT1 HCV patients (1:1:2:2) to receive either placebo or BI 201335 120 mg with three days Lead-in (LI) of PegIFN/RBV, BI 201335 240 mg QD with three days LI or BI 201335 mg 240mg QD without LI. In each treatment group, BI 201335 was given for 24 weeks together with PegIFN/RBV for 24 or 48 weeks. Patients were evaluated for SVR according to various baseline characteristics.

SILEN-C3

In this open-label Phase II trial, 159 treatment-naïve GT1 HCV patients were randomised to receive 120 mg QD BI 201335 for 12 or 24 weeks, each after three days lead-in (LI) with pegylated interferon and ribavirin (PegIFN/RBV). In both groups, PegIFN/RBV was given for 24 weeks. Patients who did not achieve an eRVR, continued PegIFN/RBV to week 48. eRVR was defined as viral load less than 25 IU/mL at week 4 and undetectable at weeks 8-18.

About Hepatitis C Virus (HCV)

HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% per year. End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.

About Boehringer Ingelheim in Virology

Boehringer Ingelheim has more than 7,500 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a longstanding history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral suspension, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.

Boehringer Ingelheim in Hepatitis C Virus (HCV)

Boehringer Ingelheim has a dedicated HCV treatment development programme, called HCVersoTM, which at its core, aims to reverse the existing HCV paradigm. The ultimate aim of this programme is to deliver improved HCV treatment outcomes for patients whilst breaking down the barriers of current treatment regimens.

BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim’s own research and development, which has completed clinical trials through Phase IIb (SILEN-C studies). This Phase II programme supports the investigation of BI 201335 in Phase III trials currently ongoing. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development.

For more information please visit www.boehringer-ingelheim.com

http://www.twitter.com/boehringer

Contacts

Boehringer Ingelheim
Corporate Communications
Media + PR
Julia Meyer-Kleinmann, +49 6132 – 77 8271
55216 Ingelheim/Germany
Fax: +49 6132 – 77 6601
press@boehringer-ingelheim.com
More information
www.boehringer-ingelheim.com

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December 9, 2011

-Studies to evaluate safety and effects on viral kinetics in people with chronic genotype-1 hepatitis C-

-Data expected in second quarter of 2012 could enable initiation of interferon-free, nucleotide-based combination studies in the second half of 2012-

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and Alios BioPharma, Inc. today announced the initiation of two clinical studies for the nucleotide analogues ALS-2200 and ALS-2158, which are inhibitors of the hepatitis C NS5B polymerase. The studies will evaluate the safety and tolerability of ALS-2200 and ALS-2158 in healthy volunteers followed by a seven-day evaluation to observe the effects on viral kinetics in people with chronic genotype-1 hepatitis C. Data are expected in the second quarter of 2012, which could enable the initiation of studies to evaluate multiple all-oral, interferon-free combination regimens for chronic hepatitis C in the second half of 2012. Vertex has worldwide development and commercialization rights for ALS-2200 and ALS-2158, which were discovered by Alios BioPharma. Alios and Vertex are jointly conducting the Phase 1 studies announced today.

"These studies are an important step in our ongoing efforts to strengthen our leadership position in hepatitis C by developing all-oral regimens that could further improve the future treatment of this disease," said Peter Mueller, Ph.D., Executive Vice President, Global Research and Development, and Chief Scientific Officer for Vertex. "The studies of ALS-2200 and ALS-2158 announced today are designed to generate data that may provide the opportunity to rapidly advance into Phase 2 development where we could evaluate a number of nucleotide-based regimens beginning in the second half of next year, including regimens with INCIVEK or VX-222."

Study Design

The two Phase 1 studies announced today will be randomized, double-blind, placebo-controlled studies. The primary goals are to evaluate the safety and tolerability of single ascending doses of ALS-2200 and ALS-2158 in healthy volunteers and of multiple ascending doses in people with chronic genotype-1 hepatitis C. A secondary objective will be to evaluate the effects on viral kinetics of ALS-2200 and ALS-2158 during seven days of dosing in people with hepatitis C.

Dosing is now underway for the study of ALS-2200, and dosing is expected to begin next week for the study of ALS-2158. Vertex and Alios BioPharma expect to have complete data, including seven-day viral kinetic data, from each trial in the second quarter of 2012, which could enable the initiation of all-oral, interferon-free Phase 2 combination studies in the second half of 2012. These Phase 2 studies are expected to evaluate combination regimens of ALS-2200 or ALS-2158 with INCIVEK (telaprevir) or VX-222, potential dual nucleotide regimens and other interferon-free combination regimens that may also include ribavirin. INCIVEK is Vertex's FDA-approved protease inhibitor for chronic genotype-1 hepatitis C, and VX-222 is Vertex's investigational hepatitis C non-nucleoside polymerase inhibitor. The combination studies will be designed to generate sustained viral response (SVR or viral cure) data.

About ALS-2200 and ALS-2158

ALS-2200 and ALS-2158 are highly potent pan-genotypic nucleotide analogues that appear in in vitro and non-clinical studies to have a high barrier to drug resistance and the potential to be dosed orally once-daily. Both compounds are designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Each compound is structurally distinct and has its own unique mechanism of action, which supports the potential for developing these compounds together as a dual nucleotide regimen and as part of combination therapy regimens, including regimens with INCIVEKTM (telaprevir) and VX-222. Data from in vitro studies showed that both ALS-2200 and ALS-2158 had a synergistic effect when combined together and with INCIVEK and VX-222. Additionally, in those in vitro studies, both compounds showed antiviral activity across all genotypes, or forms, of the hepatitis C virus, including genotypes more prevalent outside of the United States.

Vertex gained worldwide rights to ALS-2200 and ALS-2158 through an exclusive worldwide licensing agreement signed with Alios BioPharma, Inc. in June 2011. The agreement also includes a research program that will focus on the discovery of additional nucleotide analogues that act on hepatitis C polymerase. Vertex has the option to select additional compounds for development emerging from the research program.

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. Hormonal forms of birth control, including birth control pills, vaginal rings, implants or injections, may not work during treatment with INCIVEK.

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 skin reactions, rash and anemia that can be severe. 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.

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

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.

About Alios BioPharma

Alios BioPharma is a biotechnology company located in South San Francisco, California, that is developing novel medicines aimed at the treatment of viral diseases. Alios has an innovative team of highly experienced scientists and clinical researchers who are developing direct acting antiviral agents against several human viral pathogens of public health importance including, hepatotropic and respiratory viruses and other chronic, acute and emerging viral diseases. The overall goal for the Alios therapeutic platform is to maximize patient benefits in areas of high unmet medical need through optimization of potency, safety and tolerability. Alios is the recipient of the 2011 BayBio Pantheon Outstanding Partnering Award.

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 Dr. Mueller's statements in the second paragraph of this press release and statements regarding (i) the expectation that Vertex will receive data from two Phase 1 studies in the second quarter of 2012 that could enable initiation of interferon-free, nucleotide-based combination studies in the second half of 2012; (ii) the design, goals, objectives and expected timing of receiving data from the Phase 1 studies; (iii) the possible combination regimens that could be evaluated in Phase 2 studies and the potential design of such studies; and (iv) the potential for developing ALS-2200 and ALS-2158 together as a dual nucleotide regimen and as part of other combination therapy regimens. 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, the possibilities that the outcomes from the Phase 1 studies may not be favorable, that the Company may not be able to successfully develop ALS-2200 or ALS-2158, 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 the Company's website at www.vrtx.com. The Company disclaims any obligation to update the information contained in this press release as new information becomes available.

References:

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.

(VRTX-GEN)

Vertex Pharmaceuticals Incorporated
Investors:
Michael Partridge, 617-444-6108
or
Lora Pike, 617-444-6755
or
Media:
Zachry Barber, 617-444-6992
mediainfo@vrtx.com

Source: Vertex Pharmaceuticals Incorporated

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