HCV/Protease inhibitor BI 201335 and the polymerase inhibitor BI 207127

Results of Boehringer Ingelheim Oral Hepatitis C Protease Inhibitor and Polymerase Inhibitor Combination Phase Ib Trial Shows Rapid Viral Response Without Use of Pegylated Interferon
New, early-stage data evaluating investigational oral hepatitis C compounds presented at AASLD 2010 Annual Meeting

PR Newswire

BOSTON and RIDGEFIELD, Conn.,

Oct. 30, 2010

BOSTON and RIDGEFIELD, Conn., Oct. 30, 2010 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. announced today results from a Phase Ib study, SOUND-C1, that showed the combination of two oral hepatitis C virus (HCV) compounds, the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, with ribavirin reduced viral load below the lower limit of quantifiable levels in HCV treatment-naive patients. The regimen did not include interferon through the first 28 days of treatment. These data are being presented at the American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting in Boston, MA.
(Poster LB-7) New protease-polymerase inhibitor combination resulted in 73-100% rapid virological responses without pegylated interferon
In this randomized open-label trial, 32 treatment-naive genotype-1 HCV patients received BI 207127 in either 400mg or 600mg doses three times a day (TID), BI 201335 120mg once daily (QD) and ribavirin (RBV) (1000/1200mg daily in two doses) for 28 days. All patients had a rapid and sharp decline in HCV viral load during the first two days, followed by a slower second phase decline. In the lower and higher dose groups, 73 and 100% of patients achieved a rapid virological response (i.e. HCV RNA below lower limit of quantification after 4 weeks of treatment). One patient experienced a viral breakthrough (increase by >1 LOG10 from nadir during treatment) and one other experienced a 0.7 LOG10 increase in viral load. Both were in the lower dose group of BI 207127 and were patients with high baseline viral load. On day 29, all patients were switched to treatment with BI 201335 and PegIFN/RBV for an additional 44 weeks per the defined study protocol, and will be followed to evaluate sustained virological response.
"The current standard-of-care, PegIFN/RBV, is challenging for patients with chronic hepatitis C due to significant side effects that impact treatment adherence and has suboptimal response rates," said Stefan Zeuzem, MD, Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany and lead investigator of the study. "An interferon-sparing regimen could provide an important treatment option for patients with chronic hepatitis C."
Proportion of patients with viral load less then 25 IU/ml

.

.............................................................Day 8

....Day 15.....Day 22....Day 20
400mg TID BI 207127 + BI 201335 + RBV.... 4/15...6/15...10/15...11/15
600mg TID BI 207127 + BI 201335 + RBV....3/17...14/17...17/17...17/17


The PegIFN sparing treatment was well tolerated. Investigators reported that the most common adverse events observed in the study were mild gastro-intestinal effects (diarrhea, nausea, vomiting), rash or photosensitivity. Laboratory parameters did not indicate any relevant changes from baseline, except for a continuous drop in amino alanine transferase (ALT) in all patients, a decrease of hemoglobin (median -1.7 and -2.6 g/dL) and an increase of unconjugated bilirubin (median +9.8 and +11.5 umol/L) similar to reported results from earlier BI 201335 trials. There were no serious or severe adverse events and no discontinuations due to adverse events reported in the study during treatment with BI 207127 and BI 201335. A phase IIb trial testing different dose regimens of this combination with longer durations is planned to evaluate sustained virological response rates.
Additional studies to be presented at AASLD
Virological response and safety of 4 weeks treatment with the protease inhibitor BI 201335 combined with 48 weeks of peginterferon alpha 2a and ribavirin for treatment of HCV GT-1 patients who failed peginterferon / ribavirin(Poster 804. T. Berg, et al. Sun, October 31 - 8:00 AM. Hynes: Exhibit Hall C)
Genotypic and phenotypic analysis of the NS5B polymerase region from viral isolates of HCV chronically infected patients treated with BI 207127 for 5-days monotherapy.(Poster 1862. L. Lagace, et al. Tue, November 2 - 7:00 AM. Hynes: Exhibit Hall C)
The Liver Kp Corrected Inhibitory Quotient (LCIQ): A pharmacokinetic-pharmacodynamic model for direct-acting HCV antivirals(Poster 1866. J. Duan, et al. Tue, November 2 – 7:00 AM. Hynes: Exhibit Hall C)

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 indication 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 virological 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 IIb (SILEN-C studies). This Phase II program supports the investigation of BI 201335 in Phase III trials. BI 207127 is an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Planning is currently underway to begin Phase II trials of BI 207127 with BI 201335 in interferon-sparing regimens both with and without ribavirin.
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 US $17.7 billion (12.7 billion euro) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.
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