Boehringer Ingelheim enrols first patients in pivotal Phase III interferon-free hepatitis C trial programme

Today, Boehringer Ingelheim announced that the first patients have been enrolled in the company’s pivotal Phase III interferon (IFN)-free hepatitis C (HCV) clinical trial programme, HCVerso™. Boehringer Ingelheim’s IFN-free investigational polymodal* regimen combines faldaprevir (BI 201335)+, a next wave once-daily protease inhibitor, and BI 207127+, a non-nucleoside polymerase inhibitor, plus ribavirin.

The HCVerso™ clinical trial programme includes two Phase III IFN-free clinical trials that will treat approximately 1,000 treatment-naïve HCV genotype-1b (GT-1b) patients.1,2 The decision to focus the Phase III trials on this patient group follows positive Phase IIb trial data from the SOUND-C studies, where Boehringer Ingelheim’s IFN-free investigational polymodal* regimen showed high viral cure rates in patients with GT-1b HCV, the most prevalent type of HCV globally.3

New preliminary results from the SOUND-C3 trial show that 100 percent (n=20) of HCV patients with GT-1b achieved viral elimination when measured four weeks (SVR4) after completing a 16 week course of treatment. These data further support the choice of this patient population for Phase III. Full results from SOUND-C3 are expected in early 2013.

“We are proud to announce that the first patients have now been enrolled in our Phase III interferon-free clinical trial programme, HCVerso™,” said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. ““HCV patients will benefit most from an individualised treatment approach since host genetics, viral genotype and stage of liver disease vary from patient to patient. Our interferon-free investigational polymodal* regimen has shown particular promise in treating patients with genotype-1b HCV so we have decided to focus our Phase III trial programme on this population. Our goal is an interferon-free future in the treatment of HCV and ensuring all patients individually receive the most effective treatment for them.”

Results from the SOUND-C2 study, which were presented in November 2012 at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), found that up to 85 percent of GT-1b HCV patients treated with different IFN-free regimens of faldaprevir, BI 207127 and ribavirin achieved viral cure at 12 and 24 weeks following treatment completion (SVR12 and SVR24).3

Eliminating injectable interferon from treatment regimens is a critical goal in HCV as it can be challenging for patients, due to the long treatment duration and often severe side-effects. Up to 50 percent of patients may not be eligible for treatment with interferon and of those eligible, less than 80 percent of patients with the most common type of chronic HCV, genotype-1, achieve a viral cure with current interferon based triple therapies.4 The severe side-effects of interferon, including heart failure, sepsis, leukopenia, depression and vision loss, contribute to low medication adherence, ultimately leaving many patients in need uncured.5,6 Since 1999, there has been a significant increase in deaths due to chronic HCV, accounting for 15,000 deaths in the United States in 2007 alone.7

“More effective and tolerable alternatives to interferon would help patients with their decision to start and to stay on treatment, which is imperative to achieve the ultimate goal of a virologic cure,” said lead study investigator Christoph Sarrazin, M.D., Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany. “I’m pleased the trial design includes a diverse population of genotype-1b patients, particularly those with liver cirrhosis, reflecting the types of patients we see every day in clinical practice.”

Trial Designs

The HCVerso™ clinical trial programme includes two Phase III IFN-free clinical trials that will treat approximately 1,000 treatment-naïve HCV genotype-1b (GT-1b) patients. Trial sites are planned for many different countries around the world, including the US, Germany, Canada, and Australia.

HCVerso 1 1

In this Phase III study, more than 460 treatment-naïve GT-1b HCV patients will be treated. Patients will be randomised (1:1) into two treatment arms. A third, open label arm will treat up to 70 cirrhotic patients.

• Group 1: 24 weeks of BI 207127 600mg BID + faldaprevir 120mg QD + RBV
• Group 2: 16 weeks of BI 207127 600mg BID + faldaprevir 120mg QD + RBV followed by an additional 8 weeks of placebo
• Group 3 (patients with compensated liver cirrhosis): 24 weeks of BI 207127 600mg BID + faldaprevir 120mg QD + RBV

HCVerso 2 2

In this Phase III study, more than 490 treatment-naïve GT-1b HCV patients will be treated. This study includes patients who are eligible or ineligible for interferon. Patients will be randomised (1:1) into two treatment arms. A third, open-label arm will treat up to 70 cirrhotic patients.

• Group 1: 24 weeks of BI 207127 600mg BID + faldaprevir 120mg QD + RBV
• Group 2: 16 weeks of BI 207127 600mg BID + faldaprevir 120mg QD + RBV (initial 8 weeks of placebo)
• Group 3 (patients with compensated liver cirrhosis): 24 weeks of BI 207127 600mg BID + faldaprevir 120mg QD + RBV

Data from the HCVersoTM studies are expected in late 2013.

For more information regarding the trials, please visit www.clinicaltrials.gov

About HCV

HCV is a blood-borne infectious disease which lives and multiplies in the viral reservoir of the liver and is a leading cause of chronic liver disease, liver cancer and transplant. Chronic HCV is a major public health issue and one of the most prevalent infectious diseases worldwide, affecting around 150 million people, with 3-4 million new cases occurring each year.8 Only about 15-25 percent of patients clear the virus in the acute phase.8

HCV can often remain undiagnosed due to the asymptomatic nature of the disease.8 Consequently, a large number of patients first present to their physician with liver disease. Patients with advanced liver disease are challenging to cure, have the highest unmet treatment need and urgently require more effective and better tolerated options than the currently available standard of care. Of patients with chronic HCV, 20 percent will develop liver cirrhosis, of which 2-5 percent will die every year.9,10 Advanced liver disease due to HCV currently represents the main cause for liver transplantation in the western world.10

About Boehringer Ingelheim in HCV

Through pioneering science, Boehringer Ingelheim is committed to cure and ease the burden of HCV. Boehringer Ingelheim’s clinical research team is working with HCV experts to address the high unmet medical needs globally. The company is committed to developing faldaprevir (BI 201335) and BI 207127 through a rigorous clinical trial programme, designed to include a diverse population that reflects the type of real-world patients that physicians see every day in clinical practice.

Faldaprevir and BI 207127, with ribavirin are being explored as an investigational polymodal* regimen, targeting HCV through different modes of action, with the potential to improve efficacy and tolerability for HCV patients.

Faldaprevir (BI 201335), an investigational potent next wave once-daily protease inhibitor, is designed to target the viral reservoir (within the liver) and stop viral replication. Faldaprevir has completed clinical trials through Phase IIb (SILEN-C studies). The ongoing Phase III trial programme for this interferon based regimen, STARTVersoTM, that evaluates faldaprevir combined with PegIFN/RBV in treatment-naïve, treatment-experienced and HIV co-infected patients with chronic genotype-1 HCV is nearly complete.

BI 207127 is a potent investigational non-nucleoside NS5B polymerase inhibitor that when combined with faldaprevir plus ribavirin has the potential to eliminate interferon from HCV treatment. Phase II trials of this interferon-free regimen have been completed (SOUND-C2) and Phase III HCVersoTM trials investigating this regimen are underway.

* Polymodal = combining different modes of action for positive effect – as seen with faldaprevir (BI 201335), a next wave once daily protease inhibitor, and non-nucleoside polymerase inhibitor BI 207127, plus ribavirin

+ Faldaprevir and BI 207127 are investigational compounds and not yet approved. Their safety and efficacy have not yet been fully established

References

1. http://clinicaltrial.gov/ct2/show/NCT01732796?term=faldaprevir+bi+207127&rank=3
2. http://clinicaltrial.gov/ct2/show/NCT01728324?term=faldaprevir+bi+207127&rank=2
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. Ghany, Marc et al. An Update on Treatment of Genotype 1 Chronic Hepatitis C Virus Infection: 2011 Practice Guidelines by the American Association for the Study of Liver Diseases. Hepatology 2011; 54: 1433-1444
5. National Institutes of Health; US Department of Health and Human Services. Chronic Hepatitis C: Current Disease Management. Bethesda, MD: National Institutes of Health; 2010. NIH Publication 10-4230 4
6. World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 25/09/12]
7. Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012;156:271-8
8. World Health Organisation. Hepatitis C. 2012 http://www.who.int/mediacentre/factsheets/fs164/en/ [Last accessed on 04/01/13]
9. National Digestive Disease Information Clearing House, NIH. Chronic Hepatitis C Current Disease Management. NIH Publication No. 10-4230. January 2010
10. Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009