Biotech Values

[DewDiligence]

BI Reports RVR Data from All-Oral HCV Study

[BI’s all-oral HCV cocktail stands out from the others in the industry insofar as it includes ribavirin (#msg-55917807). The phase-1b study reported here tested two doses of the non-nuke, BI 207127, each in combination with the protease inhibitor, BI 201335, and a standard dose of ribavirin (http://clinicaltrials.gov/ct2/show/study/NCT01132313 ). The RVR rate was 73% in the low-dose arm and 100% in the high-dose arm; two patients in the low-dose arm had a viral rebound during the 28-day dosing period.

This study does not attempt to measure an SVR rate from all-oral therapy; instead, all patients are switched to BI 201335 + SoC after 28 days.]

http://finance.yahoo.com/news/Results-of-Boehringer-prnews-314331229.html?x=0&.v=1

›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

October 30, 2010, 9:00 am

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 <25 IU/ml

 
 Trial Arm     Day-8   Day-15   Day-22  Day-29

400mg (n=15) 27% 40% 67% 73%
600mg (n=17) 18% 82% 100% 100%
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)‹