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  EASL 48th Annual Meeting
April 24th - 28th 2013
The Netherlands, Amsterdam
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Boehringer Ingelheim announces results from one of its HCV Phase III trials: Investigational compound faldaprevir+ shows high viral cure and early treatment success in treatment-naïve patients with genotype-1 hepatitis C - press release
  · In the Phase III clinical trial STARTVerso™1, up to 80% of patients treated with faldaprevir+ and PegIFN/RBV achieved viral cure (SVR12)
· At both doses, 87 to 89% of patients met criteria to stop all treatment after 24 weeks and 86 to 89% of these patients went on to achieve SVR12 · Faldaprevir+ was well tolerated at both doses; at the lower dose side-effect related treatment discontinuation was similar to placebo For media outside USA, UK and Canada only
INGELHEIM, 23 April 2013 - Results from the pivotal Phase III STARTVerso™1 trial for the investigational once-daily protease inhibitor faldaprevir+ (BI 201335), combined with pegylated interferon α2a and ribavirin (PegIFN/RBV), in treatment-naïve patients with chronic genotype-1 hepatitis C infection, will be presented at the International Liver CongressTM (ILC) in Amsterdam this week.
The primary endpoint of the trial was sustained virological response 12 weeks after completion of treatment (SVR12).1
In STARTVersoTM1, patients who received faldaprevir+ plus PegIFN/RBV were able to stop all treatment early if their virus level was low enough at week 4 and week 8 of treatment (Early Treatment Success (ETS) as defined in the protocol*).1 ETS was achieved by 88 percent of patients treated with the faldaprevir+-based regimen. 1 These patients were eligible to stop all treatment at week 24 and 88 percent of them achieved viral cure (SVR12). In the whole study, up to 80 percent of faldaprevir+ treated patients achieved the primary end point of viral cure when measured 12 weeks after treatment was stopped (SVR12). 1 In comparison, only 52 percent of patients who received placebo plus PegIFN/RBV achieved SVR12. 1 No dose effect on efficacy was observed for faldaprevir in the study. With the lower 120mg once-daily dosing of faldaprevir+ 79 percent achieved viral cure (SVR12). Side-effect related treatment discontinuation was similar to placebo.1
"These results are encouraging as STARTVersoTM1 included a significant proportion of patients with advanced liver disease and still demonstrated an SVR12 rate up to 80 percent in patients treated with the faldaprevir+ containing regimen," Principal Investigator Professor Peter Ferenci of the Medical University Vienna pointed out. "The fact that the vast majority of patients were able to stop treatment early (after 24 weeks) and achieve viral cure along with the favourable tolerability of faldaprevir+ is very promising."
In addition, faldaprevir+ was well tolerated and adverse events that led to discontinuation of all study medications were similar to placebo (5% for 120mg faldaprevir+ treated patients vs. 4 % for placebo treated patients).1 Elevations in unconjugated bilirubin were observed in all faldaprevir+ dose groups, but these were reversible and not accompanied by increases in liver enzymes. Other changes in laboratory parameters including those relating to haemoglobin, neutrophil counts and white blood cells were also similar across all treatment arms. Anaemia (11%, 13%, 12%), rash (6%, 8%, 9%) and gastrointestinal issues (3%, 7%, 12%) were the most common Grade 2-4 adverse events in the placebo, faldaprevir 120mg and faldaprevir 240mg arms, respectively.

Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim "These Phase III results for the faldaprevir interferon-based regimen represent an important milestone as we continue to strive towards our ambition to develop a well-tolerated treatment option that considerably improves cure rates in difficult to cure genotype-1 patients. At the same time, nearly 90 percent of patients qualified for 24 weeks total treatment," said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. "Reducing the duration of interferon-based treatment means a considerable benefit in terms of quality of life - as well as providing a therapy regimen that relieves the patient from a high-pill burden and the necessity of a high fat diet intake."
The STARTVersoTM1 results are due to be presented tomorrow at the International Liver Conference™ (ILC) as part of the official press conference. In depth data will be provided by Professor Peter Ferenci during the oral presentation session Free Presentations - Parallel Sessions including Late-Breaker on Saturday, April 27, 3:30 to 5:30 pm.
More data from Boehringer Ingelheim's comprehensive trial programme in HCV
Besides STARTVersoTM1, Boehringer Ingelheim will announce more data from its comprehensive trial programme in hepatitis C at this 48th annual meeting of the European Association for the Study of the Liver (EASL) in Amsterdam.
Sub-analyses from the company's interferon-free Phase IIb SOUND-C2 study are being presented in separate abstracts which include data regarding viral response rates by level of fibrosis (abstract #1227)2, predictors of anaemia (abstract #1186)3 and pharmacokinetic modelling of the relationship between virologic response and the level of faldaprevir+ or BI 207127 found in the blood (abstract #1212)4. The SOUND-C2 trial evaluated the interferon-free combination of faldaprevir+ and BI 207127, a potent investigational non-nucleoside NS5B polymerase inhibitor, plus ribavirin.
About STARTVerso™1
STARTVerso™1 is a double-blind, placebo-controlled Phase III trial of faldaprevir+ in combination with PegIFN/RBV. The study enrolled and treated 652 treatment-naïve patients from Europe and Japan who were infected with chronic genotype-1 hepatitis C. Patients were randomised to receive a once-daily dose of 120mg faldaprevir+, 240mg faldaprevir+ or placebo in addition to PegIFN and RBV. Treatment duration depended on whether patients met criteria for protocol-defined early treatment success (ETS) (week 4 below limit of quantification [BLQ] and week 8 below limit of detection [BLD]). All patients who met these criteria received 12 weeks of faldaprevir+ with 24 weeks of PegIFN/RBV. Patients who did not meet the criteria were re-randomised to receive 24 weeks of faldaprevir+ or 12 weeks of faldaprevir+ followed by 12 weeks of placebo in the 120mg dose group or 12 weeks of faldaprevir+ in the 240mg dose group; both groups received 48 weeks of PegIFN/RBV. Patients in the control arm received 24 weeks of placebo with 48 weeks of PegIFN/RBV.
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.5 Chronic hepatitis C is a major public health issue and one of the most prevalent infectious diseases worldwide, affecting around 170 million people,6 with 3-4 million new cases occurring each year.7
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.8 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 percent will develop liver cirrhosis, of which 2-5 percent will die every year.9 Advanced liver disease due to hepatitis C currently represents the main cause for liver transplantation in the western world.9
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.
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 BI 207127 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.
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 44,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
As a central element of its culture, Boehringer Ingelheim pledges to act socially responsibly. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees 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 endeavours.
1 Ferenci, P. et al. Faldaprevir plus pegylated interferon alfa-2A and ribavirin in chronic HCV genotype-1 treatment-naïve patients: final results from STARTVerso1, a randomised, double blind, placebo-controlled Phase III trial. Presented at the International Liver CongressTM (ILC), The 48th Annual Meeting of the European Association for the Study of the Liver (EASL), 24-28 April, 2013
2 Zeuzem, S. et al. An analysis of response rates by fibrosis stage in patients treated with faldaprevir, BI 207127 and ribavirin in the SOUND-C2 study. Presented at the International Liver CongressTM (ILC), The 48th Annual Meeting of the European Association for the Study of the Liver (EASL), 24-28 April, 2013
3 Asselah, T. et al. ITPA gene variants predict haemolytic ribavirin induced anaemia in patients treated with the interferon-free regimen of faldaprevir, BI 207127 and ribavirin in SOUND-C2. Presented at the International Liver CongressTM (ILC), The 48th Annual Meeting of the European Association for the Study of the Liver (EASL), 24-28 April, 2013
4 Olsen. S. et al. Pharmacokinetic modelling of the relationship between sustained virological response and plasma concentrations of faldaprevir or BI 207127 in HCV GT1-infected patients in SOUND-C2. Presented at the International Liver CongressTM (ILC), The 48th Annual Meeting of the European Association for the Study of the Liver (EASL), 24-28 April, 2013
5 World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 16/04/12]
6 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 15/04/13]
7 World Health Organisation. Hepatitis C Fact Sheet. Updated July 2012 http://www.who.int/mediacentre/factsheets/fs164/en/index.html [Last accessed on 16/04/12]
8 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 15/04/13] 9 Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009