Boehringer Ingelheim presents interferon-free SOUND-C2 data at EASL...

Today (Saturday, April 21, 2012) is the big day all us HCV drug development nerds (I'd use 'wonks', but that sounds even worse) are waiting for in regards to the late-breaker presentations from EASL and any additional nuggets of info.  One of those presentations will  on the SOUND-C2 trial, featuring the interferon-free combination of Boehringer Ingelheim's HCV PI BI 201335 and polymerase inhibitor BI 207127 both with  ribavirin. According to the press release below, the interim results of the combo show a 68% SVR12 overall in genotype 1 patients in the 28 week arm regardless of IL-28B status. In the 16 week arm, SVR12 was achieved in 59% of patients.  As one might suspect, those subjects that were genotype 1a and non-CC IL-28B status experienced higher relapse and breakthrough rates than those who were G1b and CC.  It was also found that without the benefit of ribavirin, the subjects did substantially worse with only at 39% SVR12.  


Details are still coming, but it appears that this will be a 28 week option and the G1a non-CC patients may either need to go longer (there is a 40 week arm of this study that awaits presentation) or the addition of interferon. Ribavirin will clearly be needed in this combination as well. The odds of dosing confusion are a bit higher, with the PI boasting QD dosing and the polymerase inhibitor BID dosing.


A sub-analysis looking at the efficacy of the combination in the compensated cirrhotic was also presented in poster format. Although the numbers are small and clearly the G1b subjects respond better to the combo, it's encouraging to see any sort of SVR12 in this extremely difficult to treat population, especially without the aid of interferon.

Phase 2b Study of Boehringer Ingelheim’s Interferon-Free Hepatitis C Treatment Shows Undetectable Virus in HCV Genotype-1 Patients 12 Weeks After Treatment Ended (SVR12)

Barcelona, Spain and Ridgefield, CT, April 19, 2012 – New data from a pre-specified interim analysis of the Phase 2b SOUND-C2 study show that 68 percent of genotype-1 (GT1) hepatitis C virus (HCV) patients achieved sustained viral response 12 weeks after the end of treatment (SVR12) with Boehringer Ingelheim’s investigational direct-acting antiviral compounds – the protease inhibitor BI 201335 and polymerase inhibitor BI 207127 – plus ribavirin (RBV), without interferon. SVR12 has been highly correlated with SVR24, which is a recognized indicator of viral cure. These patients received combination therapy with BI 201335 once-daily (QD), BI 207127 twice-daily (BID) and RBV for 28 weeks. The SOUND-C2 study investigated interferon-free treatment in HCV GT1 patients, the most difficult genotype to treat, regardless of IL-28B status. Among study participants, 10 percent had compensated liver cirrhosis.

“Eliminating interferon from HCV treatment is an urgent need,” said Stefan Zeuzem, M.D., 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. “The antiviral activity of BI's all oral direct-acting antiviral compounds in the SOUND-C2 study demonstrates the potential for an interferon-free cure for HCV.”

Furthermore, a separate arm of the SOUND-C2 study showed that after 16 weeks of interferon-free treatment, SVR12 was achieved in 59 percent of patients. Investigators presented relapse data broken out by genotype and IL-28B status. The rate of relapse in the treatment arms ranged between 2 and 10 percent for GT1b and GT1a-CC patients. There was a higher rate of relapse in GT1a non-CC patients, with relapse ranging from 0 to 40 percent. The full results from this interim analysis of SOUND-C2 are being presented on Saturday, April 21, at the International Liver Congress, the 47th Annual Meeting of the European Association of the Study of the Liver (EASL 2012) in Barcelona, Spain (Abstract #101). These results supplement the abstract findings highlighted today during an official EASL press conference.

“We are looking forward to the final results from this study, that we hope will be a significant step towards an interferon-free future for patients with HCV,” said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “We are committed to the millions of people around the world who are chronically infected with HCV. Through our clinical trial program HCVersoTM, we are working with experts worldwide to ask the difficult questions that remain in HCV to find answers to the challenges that these patients face.”

Planning of the interferon-free Phase 3 clinical trial program is underway.

SOUND-C2 Pre-Specified Interim Analysis
In this open-label Phase 2b study, 362 treatment-naïve GT1 HCV patients were randomized into five interferon-free treatment groups, each with 120 mg BI 201335 QD, but with different dosing of BI 207127 and treatment durations. The randomization was stratified by HCV genotype (1a or 1b) and patient IL-28B genotype, with 41 percent of patients being GT1a and 75 percent being IL-28B CT or TT.

Investigators reported breakthrough broken out by genotype and IL-28B status. In GT1b and GT1a-CC patients, breakthrough occurred in 7 percent of patients in Arm A, 11 percent of patients in Arm B, 19 percent of patients in Arm C, 9 percent of patients in Arm D, and 29 percent of patients in Arm E (no RBV arm). In GT1a non-CC patients, breakthrough occurred in 40 percent of patients in Arm A, 50 percent of patients in Arm B, 25 percent of patients in Arm C, 64 percent of patients in Arm D, and 91 percent of patients in Arm E (no RBV arm).

In this study, the most common adverse events (AEs) were skin (photosensitivity, rash), gastrointestinal (GI) disorders (vomiting, diarrhea), and jaundice due to unconjugated hyperbilirubinemia. Treatment discontinuations due to AEs correlated with increased dosing frequency and treatment duration, with discontinuations ranging from 4.9 percent in Arm A (16 weeks) to 24.7 percent in Arm C (40 weeks). In the arm with BID dosing of BI 207127 (Arm D), discontinuations were 7.7 percent. BID dosing of BI 207127 is planned for Phase 3 investigation.