Boehringer Ingelheim’s investigational all-oral interferon-free combination achieved 95% viral cure rates in genotype-1b hepatitis C patients

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.

About Hepatitis C

Hepatitis C is a blood-borne infectious disease caused by the hepatitis C virus which lives and replicates in the liver. Hepatitis C is a leading cause of chronic liver disease, liver cancer and transplantation.2 Chronic hepatitis C is a major public health issue and one of the most prevalent infectious diseases worldwide, affecting around 170 million people,8 with 3-4 million new cases occurring each year.9

It is common for hepatitis C patients to remain undiagnosed due to the initial unspecific symptoms of the disease. Consequently, a large number of patients first present to their physician when they experience symptoms or already have liver disease.10 Patients with advanced liver disease are challenging to cure, yet have the greatest need for more effective and better tolerated treatments.

Of patients with chronic hepatitis C, 20% will develop liver cirrhosis, of which 2-5% will die every year.11 Advanced liver disease due to hepatitis C currently represents the main cause for liver transplantation in the western world.11

About Boehringer Ingelheim in hepatitis C

Through pioneering science, Boehringer Ingelheim is striving to find answers to the pressing challenges still faced by the diverse population of hepatitis C patients. The company’s comprehensively designed hepatitis C clinical trial programme includes a broad range of patients, including the challenging to cure, that clinicians see every day in clinical practice.

Boehringer Ingelheim is developing faldaprevir+, an optimised second generation protease inhibitor, as the core component for both interferon-based and interferon-free treatment regimens.

Interferon-based therapy with faldaprevir+ has the potential to improve cure rates with the added convenience of once-daily dosing and no dietary requirements for intake. Faldaprevir+ has proven efficacy in a broad range of genotype-1a and 1b hepatitis C patients. The STARTVersoTM trial programme, which includes treatment-naïve, treatment-experienced and HIV co-infected patients with hepatitis C virus, is nearly complete.

Deleobuvir+ (BI 207127) is a potent investigational non-nucleoside NS5B polymerase inhibitor, specifically optimised to treat patients with genotype-1b hepatitis C virus. Phase III HCVersoTM trials, investigating the interferon-free regimen of deleobuvir in combination with faldaprevir+ and ribavirin, are well underway.

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 is part of the company’s continued exploration to discover and develop innovative options for the treatment of HCV.

+faldaprevir is an investigational compound and not yet approved. Its safety and efficacy have not yet been fully established

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