Interferon-free combo faldaprevir+ and deleobuvir+ (BI 207127)/ribavirin achieves 95% viral cure rates in genotype-1b hepatitis C patients

 Investigational all-oral interferon-free combination from Boehringer Ingelheim achieves 95% viral cure rates in genotype-1b hepatitis C patients

Published on June 13, 2013

New data from Boehringer Ingelheim’s interferon-free SOUND-C3 study were presented during the APASL Liver Week in Singapore. The Phase IIb study investigated the efficacy and safety of faldaprevir+ and deleobuvir+ (BI 207127) plus ribavirin in treatment-naïve patients with genotype-1b (GT-1b) hepatitis C virus (HCV),1 one of the most common types of HCV globally.2

Results showed that 95% of genotype-1b (GT-1b) infected patients (19/20) who received BI’s interferon-free combination therapy achieved viral cure after 16 weeks of treatment.1 20% (4/20) of GT-1b patients in the study had liver cirrhosis (an advanced form of liver disease), all of whom achieved viral cure.1 Viral cure was defined as a sustained viral response 12 weeks after completion of treatment (SVR12).1 In contrast, patients with genotype-1a (GT-1a) infection and host IL28b type CC (n=12) had a lower viral response of 17% SVR12 (2/12), suggesting a need for treatment of greater intensity for this population and confirming the decision to focus on GT-1b patients in Phase III trials.

Eliminating injectable interferon from treatment regimens is a highly desirable goal in HCV management as it can be challenging for patients due to the long treatment duration and often severe side-effects.2 Up to 50% of patients may not be eligible for treatment with interferon and many patients who are eligible cannot tolerate the side-effects.

“These promising results indicate the potential of our interferon-free combination treatment to address an unmet medical need, and confirm our decision to focus on GT-1b patients in our pivotal Phase III interferon-free HCVerso™ trials,” said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. “The inclusion of difficult-to-cure patients such as those with liver cirrhosis and those that are interferon ineligible demonstrates the comprehensive nature of our clinical trial programme and supports our ultimate goal of making an interferon-free future a reality for HCV patients.”

In SOUND-C3, optimising treatment (by removing a deleobuvir+ first day loading dose and reducing treatment duration to 16 weeks) for GT-1b-infected patients resulting in higher efficacy compared with SOUND-C2.1 The SOUND-C2 study, presented in November 2012 at the AASLD Congress, showed viral cure rates of up to 85% with different interferon-free regimens of faldaprevir, deleobuvir+ and ribavirin in HCV GT-1b infected patients.3

Overall tolerability in the SOUND-C3 trial was good with three patients (9%) discontinuing treatment due to intolerance, and mild rash or nausea being the most common side-effects.1 Adverse events of a moderate or higher intensity were rare, with anaemia (16%), fatigue (9%), vomiting (9%) and nausea (9%) being the most frequent adverse events.1

Boehringer Ingelheim‘s pivotal Phase III interferon-free HCVerso™ programme includes three trials aiming to enrol approximately 1,100 treatment-naïve HCV GT-1b patients.4,5,6 The trial programme includes patients who are interferon ineligible and those with liver cirrhosis; results are expected in Q2 2014.
Other BI news at APASL

Results from Boehringer Ingelheim’s interferon-based Phase III STARTVerso™ trials were presented yesterday at the APASL congress by Professor Masao Omata. A post-hoc sub-analysis of patients from Asia in the STARTVerso™1 and 2 trials demonstrated that 88% (172/196) of GT-1a and GT-1b patients treated with faldaprevir (FDV 120mg or 240mg) plus PegIFN/RBV achieved viral cure compared with 62% (29/47) treated with placebo plus PegIFN/RBV.7 In addition, 94% of patients on faldaprevir were able to stop all treatments after 24 weeks of therapy.7 Currently, interferon treatment without protease inhibitors is still the standard treatment in most parts of Asia, lasting 48 weeks for GT-1 infected patients.
References

1. 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
2. World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 28/05/13]
3. Zeuzem S. et al Interferon (IFN)-free combination treatment with the HCV NS3/4A protease inhibitor BI 201335 and the nonnucleoside NS5B inhibitor BI 207127 ± ribavirin (R): Final results of SOUND-C2 and predictors of response. Abstract#232 presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), 9 – 13 November
4. 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 06/06/13]
5. 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 06/06/13]
6. ClinicalTrials.gov. BI 207127 / Faldaprevir Combination Therapy in Hepatic Impairment (Child-Pugh B) Patients With Genotype 1b Chronic Hepatitis C Infection: HCVerso3 http://clinicaltrial.gov/ct2/show/NCT01830127?term=hcverso3&rank=1 [Last accessed 06/06/13]
7. Omata, M. et al. Faldaprevir plus pegylated-interferon and ribavirin in chronic HCV genotype-1 treatment-naïve patients: subanalysis of patients from Japan, Taiwan and South Korea. Presented at APASL Liver Week, 6-10 June, 2013
8. 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 28/05/13]
9. World Health Organisation. Hepatitis C Fact Sheet. Updated July 2012 http://www.who.int/mediacentre/factsheets/fs164/en/index.html [Last accessed on 28/05/13]
10. 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 28/05/13]
11. Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009

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