EASL 2012: Viral cure achieved without interferon in up to 82% of hepatitis C patients (GT-1a & -1b*)

19 April 2012

For media outside of the U.S.A. only

Barcelona, Spain and Ingelheim, Germany [19 April 2012] – New data from the largest Phase II interferon-free trial to date, reveal that up to 82 percent of hepatitis C patients achieved a viral cure after just 28 weeks of treatment. These results were shown in specific patients infected with two prevalent types of hepatitis C (HCV) (genotypes-1a CC and -1b), following treatment with Boehringer Ingelheim’s investigational direct-acting antiviral compounds. ¹

These findings were demonstrated in the largest Phase II interferon-free trial to date, with a total of 362 patients, including those patients with advanced liver disease. The results, due to be presented on Saturday 21st April at The International Liver Congress ^TM, the 47th Annual Meeting of the European Association of the Study of the Liver (EASL) in Barcelona, supplement the abstract findings highlighted in the official EASL press office activities today. All patients in the study received treatment with the interferon-free combination of two investigational compounds, the once daily protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, both with and without ribavirin and with varying treatment durations. ¹

Of all the patients studied, including those with the hardest to cure type of hepatitis C (genotype-1a non-CC), 68 percent achieved a viral cure after 28 weeks of treatment. Most significantly, up to 82 percent of specific patients with one of the most common HCV types found across Europe and Asia (genotypes-1a CC and -1b), achieved viral cure after 28 weeks of treatment. The findings are unprecedented in this patient population and indicate the future potential of eliminating the need for interferon which still has to be administered with all current treatment options.

"Eliminating interferon from HCV treatment is an urgent need. Releasing patients from the side effects and the lengthy treatment commitment seen with interferon would be a huge advance," 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. "Such treatments would minimise the impact on patients' lives, and may encourage them to start and stay on treatment, to achieve the ultimate goal of a virologic cure."

The side effects of interferon can be severe and include heart failure, leukopenia (a decrease of white blood cells), sepsis and vision loss. ^{2, 3}

The Boehringer Ingelheim interferon-free treatment combination was generally well tolerated across the five treatment arms of the SOUND-C2 trial. Planning of the Phase III clinical trial programme is underway. This research will further investigate the efficacy and safety of the interferon-free combination therapy BI 201335 and BI 207127 in genotype-1 patients.

*HCV has at least six distinct genotypes, which are different sequences of the virus, identified by a number. Genotype-1 (GT1) patients are currently recognised as the most difficult to cure. ⁴ In addition to genotypes, there are over 50 subtypes within those genotypes, which are identified by a lowercase letter. An individual’s own genetic make-up is another factor that can determine the success of treatment, as represented by uppercase letters (for example CC, non-CC or CT).

Early viral cure is vital in HCV to minimise long term liver damage. ^3,5 Liver damage caused by HCV is the leading cause of chronic liver disease, failure, and ultimately liver transplant. ⁵

"We very much look 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 Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. "Our commitment to the millions of people around the world who are chronically infected with HCV is to deliver simpler and better tolerated solutions to treatment, including for those with traditionally difficult to cure virus types."

Other Boehringer Ingelheim data being presented at the meeting include:

• SOUND-C2 interim analysis: The efficacy and safety of the interferon-free combination of BI 201335 and BI 207127 in genotype-1 HCV patients with cirrhosis (Late breaking poster# 1420, Soriano, V et al, Thurs 19 April, 12:00-1:30 pm CEST)
• Characterisation of HCV NS3 variants that emerged during virologic breakthrough and relapse from BI 201335 Phase II SILEN-C2 study in pegylated interferon plus ribavirin treatment-experienced patients (Poster#1185, Kukolj, G et al, Sat 21 April, 12.30 – 1.30pm CEST)
• Impact of early response definitions on duration and outcome of treatment with BI 201335 plus pegylated interferon plus ribavirin (Poster# 1209, Sulkowski, M et al, Sat 21 April, 12.30 – 1.30pm CEST)
• Preclinical characterisation of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BI 207127 (Poster# 822, Beaulieu, P.L. et al, Fri 20 April, 12.30 – 2.00pm CEST)

NOTES TO EDITORS

Results of this open-label, randomised, Phase IIb study were presented as an oral presentation of the abstract titled "SVR4 and SVR12 with an interferon-free regimen of BI 201335 and BI 207127, +/- ribavirin, in treatment-naïve patients with chronic genotype-1 HCV infection: Interim results of SOUND-C2", by Professor Stefan Zeuzem. In the Phase IIb study, 362 treatment-naive GT1 HCV patients were randomised into five interferon-free treatment groups, each with 120mg BI 201335 once daily but with different dosing and treatment durations of BI 207127 as follows:

• BI 201335 120mg (once-daily) QD + BI 207127 600mg (three times daily) TID + RBV for 16 weeks;
• BI 201335 120mg QD + BI 207127 600mg TID + RBV for 28 weeks;
• BI 201335 120mg QD + BI 207127 600mg TID + RBV for 40 weeks;
• BI 201335 120mg QD + BI 207127 600mg BID (twice daily) + RBV for 28 weeks;
• BI 201335 120mg QD + BI 207127 600mg TID without RBV for 28 weeks.

About Hepatitis C Virus (HCV)
Hepatitis C is a viral disease caused by the hepatitis C virus (HCV) that mainly affects the liver. It is a leading cause of chronic liver disease and liver transplant. The number of individuals chronically infected with HCV globally has been estimated at 170 million, with 3–4 million new infections occurring each year. Only about 20–45 percent of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20 percent will develop cirrhosis within 20 years on average. The mortality rate after cirrhosis has developed is 2-5 percent per year. End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.

About Boehringer Ingelheim in Virology
Boehringer Ingelheim has more than 7,500 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to the ongoing research programme for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including discovery of the first HCV protease inhibitor and compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral solution, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, the first approved second generation HIV protease inhibitor). The company has a well established research centre in Laval, Canada, dedicated to virology research since the early 1990’s, and is committed to developing new therapies for virological diseases with a high unmet medical need.

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
Boehringer Ingelheim has a long-standing commitment to virology, including developing innovative therapies for HIV/AIDS and HCV. Through pioneering science, Boehringer Ingelheim strives to spread the cure in HCV and ease the burden of the disease. Boehringer Ingelheim’s clinical research team is working with HCV experts from all over the world to extend a cure to more patients suffering from the disease, including those who are toughest to cure. Boehringer Ingelheim is investigating BI 201335 and BI 207127 through HCVerso ^TM, our rigorous clinical trial program that is designed to find answers to the challenges that HCV patients face.

BI 201335, an investigational oral HCV NS3/4A next generation protease inhibitor that has the potential to improve cure rates as compared to PegIFN/RBV therapy alone, has completed clinical trials through Phase IIb (SILEN-C studies). A multi-study Phase III trial programme currently is underway to evaluate BI 201335 combined with PegIFN/RBV in treatment-naïve, treatment-experienced and HIV co-infected patients with chronic genotype-1 HCV.

BI 207127, an investigational NS5B RNA-dependent polymerase inhibitor that has the potential to eliminate interferon from HCV treatment when combined with BI 201335 and RBV, is currently being investigated in Phase II trials in interferon-sparing regimens.

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Equal opportunities for all employees and involvement in social projects, such as providing VIRAMUNE® free of charge in developing countries, form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24 percent of net sales in its largest business segment Prescription Medicines on research and development.

Updated information on the corporation’s annual results in 2011 will be available on April 24th, 2012.

For more information please visit www.twitter.com/boehringer

Backgrounder:

• Hepatitis C Virus (HCV)
• Research & Development in Hepatitis C
• Boehringer Ingelheim HCV Clinical Trials Overview

References
¹Zeuzem S et al. SVR4 and SVR12 with an interferon-free regimen of BI 201335 and BI 207127 +/- ribavirin, in treatment-naive patients with chronic genotype-1 HCV infection. Abstract#101 presented at the International Liver CongressTM (ILC), 18 -22 April 2012
²National 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.
³World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 16/04/12]
⁴Ghany, M. 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, August 2011.
⁵About.com. 2009. What Is a Sustained Virologic Response or "SVR"? http://hepatitis.about.com/od/treatment/f/SVR.htm [Last accessed on 16/04/12]

A measure of Sustained Viral Response (SVR) is considered viral cure. SVR has recently been defined by the FDA as undetectable hepatitis C virus 12 weeks after treatment has been completed (SVR12).

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