Boehringer Ingelheim completes patient enrolment of two pivotal Phase III interferon-free hepatitis C clinical trials

Aug 15 2013

Boehringer Ingelheim today announced that enrolment of over 950 treatment naïve genotype-1b patients in the pivotal Phase III interferon-free HCVerso™ 1 and 2 trials is complete.^1,2  The trials are investigating the efficacy and safety of Boehringer Ingelheim’s second generation protease inhibitor faldaprevir* and NS5B polymerase inhibitor deleobuvir (BI 207127)*, in combination with ribavirin. HCVerso™ 1 and 2 include difficult-to-treat patient populations such as those who are ineligible for interferon or those with liver cirrhosis.

This important developmental milestone coincides with today’s publication of Boehringer Ingelheim’s Phase IIb interferon-free SOUND-C2 study in the New England Journal of Medicine (NEJM). ³ SOUND-C2 showed viral cure rates (sustained virological response, SVR) of up to 85% in patients infected with genotype-1b (GT-1b) hepatitis C virus (HCV). SOUND-C2 investigated the efficacy and safety of faldaprevir* and deleobuvir* plus ribavirin in treatment-naïve patients with genotype-1a and 1b HCV, the most common types of HCV globally. The study included patients with liver cirrhosis (9%), who showed similar rates of viral cure as patients without cirrhosis.⁴

“We are proud to announce the completion of patient recruitment in two of our pivotal HCVerso™ trials. This is an important step towards our goal of delivering an effective and well tolerated cure that will enable patients and doctors to consider an individualised approach for interferon-free HCV therapy,” said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. “The publication of the SOUND-C2 study in the NEJM as well as the speedy recruitment into our pivotal trials provide an indication of the high relevance of interferon-free regimens for the future treatment of HCV. We look forward to the first Phase III results of faldaprevir*, deleobuvir* plus ribavirin in 2014 and the opportunity to explore wider patient populations in the future.” 

Results from the Phase IIb SOUND-C3 study were also recently presented at the APASL Liver Meeting in Singapore. This follow-up study to SOUND-C2 aimed to further optimise the dosing regimen containing faldaprevir* and deleobuvir* plus ribavirin in treatment-naïve patients (including patients with cirrhosis and those who could not tolerate interferon). SVR rates of 95% were observed in GT-1b infected patients after 16 weeks of treatment.⁵ The regimen tested in the SOUND-C3 study is now under Phase III evaluation in the HCVerso™ 1 and 2 trials.

Overall tolerability in the SOUND-C trials was good. In the dose-finding study SOUND-C2, 44 of the 362 patients included in the analysis discontinued due to adverse events. ³ In SOUND-C3, mild rash and nausea were the most common side-effects. Adverse events of a moderate or higher intensity were rare, with anemia (16%), fatigue (9%), vomiting (9%) and nausea (9%) being the most frequent adverse events.⁵

The decision to focus on GT-1b in HCVerso™1 and 2 was based on the higher efficacy seen in this population compared to GT-1a infected patients in the SOUND-C studies (SVR12 in GT-1a patients in SOUND-C2 and SOUND-C3: 58/148 and 2/11 of patients, respectively).³

As part of Boehringer Ingelheim’s long-term commitment to hepatitis C, the company is also evaluating other combinations of investigational hepatitis C compounds that work in different ways. Boehringer Ingelheim’s recent collaboration with Presidio Pharmaceuticals, Inc. for a Phase II clinical study investigating an interferon-free, all-oral combination in GT-1a is part of the company’s continued exploration to discover and develop innovative options for the treatment of HCV.

For more information please visit www.boehringer-ingelheim.com

References

1. ClinicalTrials.gov. IFN-free Combination Therapy in HCV-infected Patients Treatment-naive:HCVerso1. http://clinicaltrial.gov/ct2/show/NCT01732796?term=faldaprevir+bi+207127&rank=3 [Last accessed 12/07/13]
2. ClinicalTrials.gov. Phase 3 Study of BI 207127 in Combination With Faldaprevir and Ribavirin for Treatment of Patients With Hepatitis C Infection, Including Patients Who Are Not Eligible to Receive Peginterferon: HCVerso2. http://clinicaltrial.gov/ct2/show/NCT01728324?term=faldaprevir+bi+207127&rank=2 [Last accessed 12/07/13]
3. Zeuzem, S. et al. Faldaprevir and Deleobuvir for HCV Genotype 1 Infection. New England Journal of Medicine. 2013; 369 (7); 630-639 [Available online at: http://www.nejm.org/doi/full/10.1056/NEJMoa1213557]
4. Soriano V. et al. Efficacy and safety of the interferon (IFN)-free combination of BI 201335 + BI 207127 ± ribavirin (RBV) in treatment-naïve patients with HCV genotype (GT) 1 infection and compensated liver cirrhosis: Results from the SOUND-C2 study. Abstract#84 presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), 9 – 13 November
5. Zeuzem, S. et al. Interferon-Free Treatment with Faldaprevir, BI207127 and Ribavirin in SOUND-C3: 95% SVR12 in HCV-GT1b. Presented at APASL Liver Week, 6-10 June, 2013
6. World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 16/07/13]
7. Centers for Disease Control and Prevention (2012) Hepatitis C available at: http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/hepatitis-c.htm [Last accessed on 16/07/13]
8. World Health Organisation. Hepatitis C Fact Sheet. Updated July 2012 http://www.who.int/mediacentre/factsheets/fs164/en/index.html [Last accessed on 16/07/13]
9. Chen S.L., Morgan T.R. The Natural History of Hepatitis C Virus (HCV) Infection. Int J Med Sci 2006; 3:47-52. Available from http://www.medsci.org/v03p0047.htm [Last accessed on 16/07/13]
10. Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009