Positive Phase 2 Results Reported with Boehringer Ingelheim Corporation’s Investigational HCV Protease Inhibitor in Both Previously Treated and Untreated Patients

BERLIN and RIDGEFIELD, Conn., April 1, 2011 /PRNewswire/ -- New data presented today at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) demonstrate the antiviral activity of Boehringer Ingelheim’s once-daily oral protease inhibitor, BI 201335, in both treatment-naive and -experienced patients with chronic genotype-1 (GT1) hepatitis C virus (HCV), the most challenging genotype of HCV to treat. Results from SILEN-C1 show a sustained viral response (SVR) in 71 to 83 percent of treatment-naive patients who received BI 201335 once-daily plus the current standard-of-care (SOC) [pegylated interferon (PegIFN) and ribavirin (RBV)].

Results from SILEN-C2 show an SVR in 28 to 41 percent of treatment-experienced patients who received BI 201335 once-daily plus PegIFN and RBV.

“SILEN-C1 and 2 have shown positive Phase 2 results in a broad range of HCV patients,” said Peter Piliero, M.D., executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “The current standard-of-care in HCV is not effective for enough patients. Protease inhibitors such as BI 201335 represent potential new options to improve outcomes and the possibility to shorten the duration of treatment for HCV disease.”

“Boehringer Ingelheim is continuing its long heritage in virology and commitment to develop new medicines for HCV,” continued Piliero. “BI 201335 is part of BI’s growing HCV portfolio, which is being investigated with the goal of improving treatment and cure rates for HCV patients. We are excited that we will commence our Phase 3 trial program with BI 201335 in the near future, based on the results of these Phase 2 studies.”

(Oral abstract #60) SILEN-C1: Sustained Virologic Response (SVR) and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Patients with Chronic Genotype-1 HCV Infection

In this double-blind, randomized, placebo-controlled trial, 429 treatment-naive genotype-1 (GT-1) HCV patients were randomized (1:1:2:2) to receive either:

• Placebo plus PegIFN/RBV;
• BI 201335 120mg once-daily (QD) with a three-day LI of PegIFN/RBV;
• BI 201335 240mg QD with a three-day LI of PegIFN/RBV; or
• BI 201335 240mg QD plus PegIFN/RBV without LI

Patients were given BI 201335 for 24 weeks in combination with PegIFN/RBV, which was given for 24 or 48 weeks. Patients in the two BI 201335 240mg QD groups who achieved extended rapid virological response (eRVR, defined as plasma viral load less than 25 IU/ml at Week four and undetectable at Weeks 8-20), were re-randomized to discontinue PegIFN/RBV at Week 24 or continue PegIFN/RBV to Week 48.

Overall SVR rates reached 83 percent in the 240mg QD group (plus current SOC). A three-day lead in with SOC prior to initiation of BI 201335 was seen to reduce responses by 12 percent and 10 percent in 120mg QD/LI and 240mg QD/LI patient groups. The LI was also associated with higher rates of viral breakthrough. Of the patients in the 240mg QD dose group who achieved extended rapid viral response (eRVR, defined as plasma viral load less than 25 IU/ml at Week four and Weeks 8-20) and were re-randomized at Week 24, 93 percent achieved SVR with 24 weeks of SOC (PegIFN/RBV) treatment.

The most frequent dose-dependent adverse events (AEs) in BI 201335 treatment groupswere gastrointestinal disorders, rash or photosensitivity, and jaundice resulting from isolated unconjugated hyperbilirubinemia. Average alanine aminotransferase (ALT) improved in all BI 201335 groups compared to placebo, and there was no excess anemia reported in the study. Across BI 201335 treatment groups, 4 to 12 percent of patients discontinued BI 201335 due to AEs.

(Oral abstract #66) SILEN-C2: Sustained Virologic Response and Safety of BI 201335 Combined with Peginterferon Alfa-2a and Ribavirin in Chronic HCV Genotype-1 Patients with Non-Response to PegIFN/RBV

The SILEN-C2 study evaluated the virological response and safety of different doses of BI 201335 in treatment-experienced patients who did not respond to at least 12 weeks of prior treatment with PegIFN/RBV. This patient population is particularly difficult to treat, as patients who have not responded to PegIFN/RBV alone have low response rates to additional treatments. The trial did not include patients who relapsed after initial treatment with PegIFN/RBV.

In this double-blind, randomized, placebo-controlled trial, 288 treatment-experienced GT-1 HCV patients were randomized (2:1:1) to receive either:

• BI 201335 240mg QD with a three-day LI of PegIFN/RBV;
• BI 201335 240mg QD plus PegIFN/RBV without LI; or
• BI 201335 240mg twice-daily (BID) with a three-day LI of PegIFN/RBV

In each group, patients were given BI 201335 for 24 weeks in combination with PegIFN/RBV, which was given for 24 or 48 weeks.

Patients in the two BI 201335 QD groups who achieved eRVR were re-randomized to either stop all treatment at Week 24 or continue PegIFN/RBV until Week 48.

BI 201335 once-daily at 240mg plus SOC provided positive Phase 2 results in this very difficult-to-treat patient population. As is seen in SILEN-C1, a three-day LI with SOC was associated with decreased viral response. Phase 3 trials of BI 201335 are in preparation.

The most frequent dose-dependent AEs in BI 201335 treatment groups were gastrointestinal disorders, jaundice resulting from unconjugated hyperbilirubinemia, and mild to moderate rash or photosensitivity. Serious or severe AEs were reported more frequently in the BI 201335 240mg BID with LI group. Discontinuations due to adverse events ranged from 4 percent in the BI 201335 240mg QD without LI group to 23 percent in the BI 201335 240mg BID with LI group.

Additional HCV Studies to be Presented at EASL

• SVR and pharmacokinetics of the HCV protease inhibitor BI 201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV
  (Poster #1231. S. Pol, et al., April 2, 9:00 a.m.-6:00 p.m. CET)
• Mechanisms of isolated unconjugated hyperbilirubinemia induced by the HCV NS3/4A protease inhibitor BI 201335
  (Poster #1236. R. Sane, et al., April 2, 9:00 a.m.-6:00 p.m. CET)
• BI 201335 pharmacokinetics and early effect on viral load in HCV genotype-1 patients
  (Poster #1249. C. Yong, et al., April 2, 9:00 a.m.-6:00 p.m. CET)
• Preclinical characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941
  (Poster #1215. G. Kukolj, et al., April 2, 9:00 a.m.-6:00 p.m. CET)

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 three to four million new infections occurring each year. Only about 20-45 percent of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20 percent will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is two to five percent 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 6,900 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 long-standing history in virology drug development, including compounds for the treatment of HIV. The company has a well established research center in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virologic diseases with a high unmet medical need.

Boehringer Ingelheim in Hepatitis C Virus (HCV)

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 2b (SILEN-C studies). This Phase 2 program supports the investigation of BI 201335 in Phase 3 trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase 1 clinical trials. Phase 2 trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.

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 142 affiliates in 50 countries and more than 41,500 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.

In 2009, Boehringer Ingelheim posted net sales of U.S. $17.7 billion (12.7 billion euro) while spending 21 percent of net sales in its largest business segment, Prescription Medicines, on research and development.

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