Sustained Viral Response from Phase 2 Studies of BI 201335, Including Difficult-to-Treat HCV Patient Types

SAN FRANCISCO and RIDGEFIELD, Conn., Nov. 8, 2011 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced results from two Phase 2 studies evaluating the combination of the company's protease inhibitor, BI 201335, with pegylated interferon (PegIFN) and ribavirin (RBV) in treatment-naive genotype-1 (GT1) hepatitis C virus (HCV) patients.  The results from the SILEN-C3 and SILEN-C1 studies show that BI 201335 may have the potential to shorten the duration of treatment compared to PegIFN/RBV for a large portion of patients, as well as improve the likelihood of viral cure for patients with characteristics that make their HCV more difficult to treat.  These data were presented in oral sessions at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, CA.  Phase 3 studies evaluating BI 201335 in various regimens and patient types are ongoing.

"Shortening the length of treatment is among the goals we have at Boehringer Ingelheim as we seek to innovate a new treatment option for HCV patients.  We are encouraged to see that the SILEN-C3 study results suggest that treatment with BI 201335 beyond 12 weeks may not be needed for treatment-naive patients who had an extended rapid viral response," said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc.  "The SILEN-C1 subgroup results from the more difficult-to-treat patient types also are promising.  We look forward to results from our ongoing Phase 3 program with BI 201335."

(Abstract #36) SILEN-C3:  Treatment for 12 or 24 Weeks with BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin (P/R) in Treatment-Naive Patients with Chronic Genotype-1 HCV Infection

The results from SILEN-C3 indicate that among patients who had an extended rapid viral response (eRVR), 12 weeks of treatment with BI 201335 on the background of 24 weeks of PegIFN/RBV was sufficient to achieve sustained viral response (SVR).  Patients with undetectable viral load prior to week 8 had similar SVR rates, whether they were treated for 12 or 24 weeks with BI 201335 (80 percent and 82 percent, respectively).

The most frequent adverse events (AEs) in SILEN-C3 were mild gastrointestinal disorders, rash, photosensitivity and jaundice due to isolated unconjugated hyperbilirubinemia.

In this open-label Phase 2 trial, 159 treatment-naive GT1 HCV patients were randomized to receive 120 mg BI 201335 once daily for 12 or 24 weeks, each after three days lead-in (LI) with PegIFN/RBV.  In both groups, PegIFN/RBV was given for 24 weeks.  Patients who did not have 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.  In the 12 week treatment group, 72 percent of patients had an eRVR and in the 24 week treatment group, 82 percent of patients had an eRVR.

(Abstract #226) Treatment with the 2nd Generation HCV Protease Inhibitor BI 201335 Results in High and Consistent SVR Rates – Results from SILEN-C1 in Treatment-Naive Patients Across Different Baseline Factors

This analysis of SILEN-C1 evaluated SVR according to various baseline characteristics among patients who received BI 201335 240 mg once daily without LI.

The majority of patients with more difficult-to-treat HCV types – specifically GT1a and IL-28B non-CC allele patients – achieved SVR.  Among patients with GT1a HCV (n=32), a type that traditionally is associated with lower treatment response rates compared to GT1b, 82 percent achieved SVR.  Among GT1b HCV patients (n=38), 84 percent achieved SVR.  In addition, SVR was 71 percent for patients with non-CC alleles of the IL-28B gene (n=29).  Patients with CC alleles (n=11) or for whom IL-28B genotyping was missing (n=31) achieved 100 percent and 86 percent SVR, respectively.  IL-28B is a gene that is an important predictor of the likelihood of response to HCV treatment.  Patients with non-CC alleles of IL-28B are less likely to achieve SVR with PegIFN/RBV treatment.  A previously presented analysis of SILEN-C1 showed there was no benefit of PegIFN/RBV LI dosing.

SILEN-C1 is a double-blind, randomized, placebo-controlled trial that randomized 429 treatment-naive GT1 HCV patients (1:1:2:2) to receive either placebo or BI 201335 120 mg with three days LI of PegIFN/RBV, BI 201335 240 mg once daily with three days LI or BI 201335 240 mg once daily without LI.  In each treatment group, BI 201335 was given for 24 weeks together with PegIFN/RBV for 24 or 48 weeks.  SVR results from all SILEN-C1 study groups were previously presented at the 46^th Annual Meeting of the European Association for the Study of the Liver (EASL) in April 2011.

In SILEN-C1, the most frequent dose-dependent AEs in BI 201335 treatment groups were gastrointestinal disorders, rash, photosensitivity and jaundice resulting from isolated unconjugated hyperbilirubinemia.

About Hepatitis C Virus

HCV is an infectious disease of the liver and is a leading cause of chronic liver disease, transplant and failure that affects as many as 175 million people globally, with three to four million new infections occurring each year.  In the United States, an estimated 4.1 million Americans have been infected with HCV, of whom approximately 3.2 million have chronic HCV infection.  Chronic HCV infection is the cause of an estimated 8,000 to 10,000 deaths annually in the United States.  The majority – about 75 to 85 percent – of HCV cases will develop into chronic infection.  It is estimated 20 percent of patients with chronic HCV will develop cirrhosis within 20 years of infection.  The mortality rate after cirrhosis has developed is 2 to 5 percent per year.

About Boehringer Ingelheim in Hepatitis C Virus

Boehringer Ingelheim has a long-standing commitment to virology, including developing innovative therapies for HIV/AIDS and HCV.  The company recognizes the significance of the HCV epidemic and continues to work on improving treatment and cure rates for diverse populations of HCV patients through its dedicated HCV treatment development program, called HCVerso™.

Boehringer Ingelheim is advancing BI 201335, an investigational oral HCV NS3/4A protease inhibitor that has the potential to improve cure rates as compared to PegIFN/RBV therapy.  A multi-study Phase 3 trial program currently is underway to evaluate BI 201335 combined with PegIFN/RBV in both treatment-naive and -experienced patients with chronic genotype-1 HCV.

Boehringer Ingelheim also is developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has the potential to eliminate interferon from HCV treatment when combined with BI 201335 and RBV. Phase 2 trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, with and without RBV, are currently underway.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

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.

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SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.