Thursday, April 19, 2012

EASL- First ever data investigating interferon-free treatment in hepatitis C patients who have liver cirrhosis shows high viral cure rate: protease inhibitor BI 201335 plus the polymerase inhibitor BI 207127 plus ribavirin

First ever data investigating interferon-free treatment in hepatitis C patients who have liver cirrhosis shows high viral cure rate: protease inhibitor BI 201335 plus the polymerase inhibitor BI 207127 plus ribavirin (Boerhinger Ingelheim)

Barcelona, Spain and Ingelheim, Germany [19 April 2012] - New data from the SOUND-C2 study shows that up to 71 percent of patients with hepatitis C and liver cirrhosis achieved a viral cure, after just 28 weeks of treatment. These patients, who had a prevalent type of hepatitis C virus (genotype-1b), received interferon-free treatment with Boehringer Ingelheim's investigational direct-acting antiviral compounds - namely the protease inhibitor BI 201335 plus the polymerase inhibitor BI 207127 plus ribavirin.

Treatment options for hepatitis C virus (HCV) in patients with liver cirrhosis are highly underresearched, despite the urgent medical need. These new data are the first to demonstrate viral cure using an interferon-free treatment specifically in cirrhotic hepatitis C (HCV) patients, and show the potential for significantly shorter treatment duration. These findings are considered relevant for the 20 percent of chronic HCV patients who develop cirrhosis, an estimated 34 million people worldwide. 2

Presented today at the International Liver Congress TM, the 47 th Annual Meeting of the European Association of the Study of the Liver (EASL) in Barcelona, these results are from one of five treatment arms within the largest Phase II interferon-free HCV study to date (SOUND-C2). This study investigated the combination of the once daily protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, without interferon and both with and without ribavirin, and with varying treatment durations. 1

Liver cirrhosis, described as when dying liver cells are replaced by scar tissue, causes liver function to deteriorate over time and increases the risk of liver cancer and the need for a liver transplant. 3

"Patients with cirrhosis are in urgent need of effective treatment options that achieve a viral cure before the liver is incapable of maintaining its liver function. Often these patients cannot tolerate interferon-based treatment," 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 one of the study investigators. "These results show great potential and hope for achieving viral cure in advanced HCV patients without the burden of interferon and warrant further evaluation of this regimen."

Eliminating interferon from HCV treatment is vital to combat the serious burden of significant side effects. Interferon is a component of all currently available treatment options and side effects can include heart failure, sepsis, leukopenia (a decrease of white blood cells) and vision loss. 3,4

Genotype-1 (GT1a and GT1b) is the most prevalent form of HCV, and also the hardest to cure with interferon based regimens. 5 In addition, patients with liver cirrhosis have historically responded poorly to treatment, particularly interferon. 6 However, these results show that up to 71 percent of cirrhotic patients with GT1b achieved viral cure (SVR12) after 28 weeks of interferon-free treatment. 1 Data from other non-cirrhotic patient groups within this study, SOUND-C2, are highlighted in the official EASL press office activities today and will be presented in full on Saturday April 21, at the International Liver Congress TM.

"This data shows promise for treating HCV patients with advanced disease," said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. "The cirrhotic patient population had not been evaluated in an interferon-free trial before, further demonstrating Boehringer Ingelheim's commitment to providing a simpler cure to all those suffering from HCV, even the patients which present with the most challenge to treatment."

Other Boehringer Ingelheim data being presented at the meeting include:

· 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 (Abstract#101, Zeuzem, S et al, 21 April 2012, 8.30 - 8.45 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 sub-anaylsis of the open-label, randomised, Phase IIb study were presented as a poster of the abstract titled "The efficacy and safety of the interferon-free combination of BI 201335 and BI 207127 in genotype 1 HCV patients with cirrhosis- interim analysis from SOUND-C2", by Dr. Vincent Soriano.

SOUND C2 is a Phase IIb study with five treatment groups. Treatment-naive HCV (GT1) patients received 120mg BI 201335 once daily but with different dosing and treatment durations of BI 207127. Patients were randomised into one of the five interferon-free treatment groups, 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.

37 cirrhotic patients were included in this sub-analysis of SOUND C2. Patients were randomised to 1 of the 5 treatment groups above. Results above are representative of patients treated with BI 201335 120mg QD + BI 207127 600mg BID (twice daily) + 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.


1 Soriano V. The efficacy and safety of the interferon-free combination of BI 201335 and BI 207127 in genotype-1 HCV patients with cirrhosis. Poster #1420 presented at the International Liver CongressTM (ILC), 18 -22 April 2012

2The Body. Access to Hepatitis C Treatment: A Global Movement Gains Momentum [Last accessed on 16/04/12]

3 HCVAdvocate. What is Cirrhosis? [Last accessed on 16/04/12]

4 World Health Organisation. Hepatitis C. 2002 [Last accessed on 16/04/12]

5 Ghany, 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.

6 Wright, T. Treatment of Patients With Hepatitis C and Cirrhosis.Hepatology, 2002; 36 (Suppl.5b), S185-S194

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).

Also see:EASL-BI 201335 and BI 207127-Viral cure achieved without interferon in up to 82% of hepatitis C patients (GT-1a & -1b*)

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