Boehringer to present data of SOUND-C1 Phase Ib study for HCV treatment at AASLD Meeting

Nov 1 2010

Boehringer Ingelheim announced 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 to the lower limit of quantifiable levels in HCV treatment-naïve 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.

“These early data suggest that there is the potential for the combination of oral anti-HCV therapies to reduce the viral load in a more tolerable, interferon-sparing regimen. The current standard-of-care, PegIFN/RBV, is challenging for HCV patients due to side effects that impact treatment adherence and has suboptimal response rates”

(Poster LB-7) New protease-polymerase inhibitor combination resulted in 73-100% rapid virological responses without pegylated interferon
In this randomised open-label trial, 32 treatment-naïve genotype-1 HCV patients received a combination of BI 207127 in either 400mg or 600mg doses three times a day (TID) with BI 201335 120mg once daily (QD) together with 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. had a HCV RNA below thelower 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 patients were in the lower dose group of BI 207127 and were patients with a 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.

"These early data suggest that there is the potential for the combination of oral anti-HCV therapies to reduce the viral load in a more tolerable, interferon-sparing regimen. The current standard-of-care, PegIFN/RBV, is challenging for HCV patients due to 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

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, 2 November 2 - 7:00 AM. Hynes: Exhibit Hall C)

Source: Boehringer Ingelheim