Boehringer Ingelheim enrolls final patient in BI 210335 HCV protease inhibitor phase III trial....

The race for the 2nd generation of HCV Direct Acting Antivirals continues to be too close to call, with BI's BI 210335 HCV protease inhibitor finalizing it's last patient for it's phase III trial. The asute observer of the HCV marketplace will recall the interim results of BI's SOUND-C2 trial looking at the interferon-free combo of BI 201335 and BI's BI 207127 polymerase inhibitor in genotype 1 tx-naive patients. At week 12, 76% of patients had VR with a respectable 63% of patients achieved SVR12.


From Medical News Today

Boehringer Ingelheim Completes Patient Entry For Phase III Trial Program In Hepatitis C
12 Dec 2011

According to Boehringer Ingelheim's announcement, the company's large-scale Phase III clinical trial program for BI210335, an investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV) has randomized the final patient for treatment.

Their current extensive trial program is conducted in 15 countries, with key regions in the E.U., Japan, the U.S., Canada, Korea, Taiwan and Russia at over 350 sites and involves almost 2,000 treatment-experienced and treatment-naïve patients overall.

The program's three Phase III trials will be carried out to assess BI 201335 combined with the golden standard treatment of pegylated interferon (pegIFN) and ribavirin (RBV) in patients with chronic genotype-1 HCV. The majority of HCV patients infected with the genotype 1 virus are amongst the most difficult patient groups to treat. The study program's primary clinical endpoint is the assessment of "sustained viral response" (SVR), considered to be a viral cure, with results from the Phase III trials expected in the first half of 2013.

The complete BI 201335 program was awarded a Fast Track designation by the FDA. The U.S. Food and Drug Administration has designed the Fast Track process to enable the development and review process of important new drugs to treat serious diseases more rapidly than usual to fill an unmet medical need.

Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim said: "We are progressing our BI 201335 program with a high priority to leverage its potential to improve cure rates in HCV treatment. We believe our HCV-pipeline may become an important tool to fight a chronic disease that affects over 170 million people worldwide."

Last month at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, USA, Boehringer Ingelheim presented findings of their Phase IIb trial, which demonstrated that the interferon-free combination of BI 201335, with their polymerase inhibitor BI 207127 (SOUND-C2) resulting in 76% of patients achieving a virological response at week 12 and 63% of patients achieved SVR12, an undetectable virus 12 weeks after treatment, at week 16.

In addition to their BI 201335 results, the company also presented their SILEN-C1 and SILEN-C3 study results at the AASLD, demonstrating that BI 201335/ PegIFN/RBV's potentially shortens the time of treatment and improves the likelihood of viral cure (SVR). These Phase IIb results provide a strong case for further development, whilst BI 201335 continues its progress through Phase III.

Written by: Grace Rattue

Boehringer Ingelheim BI 201335 and BI 207127 data to be presented at AASLD...

BI releases it's oral and poster presentation coverage for AASLD. Hot on the list will be SOUND-C2, a phase IIb study looking at an interferon-free combo regimen of BI's polymerase inhibitor BI 2071287 and protease inhibitor BI 201335 both with and without ribavirin.


Boehringer Ingelheim announces new data from hepatitis C virus portfolio

Published on October 22, 2011 at 12:58 AM

Boehringer Ingelheim announced today that new data from its hepatitis C virus (HCV) portfolio will be presented in scientific sessions at The Liver Meeting® 2011, the 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place November 4 - November 8 in San Francisco, CA. The abstracts are published online at www.aasld.org.

Key data presented will include a week 12 interim analysis of SOUND-C2, a Phase IIb study evaluating an interferon-free combination of its protease inhibitor BI 201335 and its polymerase inhibitor BI 207127 - with and without ribavirin in treatment-naïve HCV infected patients. In addition, SILEN-C1 and SILEN-C3 data will further assess the efficacy and safety of BI 201335 in treatment-naïve HCV-infected patients, in combination with pegylated interferon alfa-2a and ribavirin (PegIFN/RBV).

SOUND-C2
In SOUND-C2, 362 treatment-naïve patients with chronic genotype-1 HCV infections were randomised into five interferon-free treatment arms, each with 120mg BI 201335 once daily (QD) but with different dosings of BI 207127 and ribavirin as follows:
• 120 mg QD BI 201335 combined with 600 mg TID (thrice daily) BI 207127 and RBV for 16 weeks
• 120 mg QD BI 201335 combined with 600 mg TID BI 207127 and RBV for 28 weeks
• 120 mg QD BI 201335 combined with 600 mg TID BI 207127 and RBV for 40 weeks
• 120 mg QD BI 201335 combined with 600 mg BID (twice daily) BI 207127 and RBV for 28 weeks
• 120 mg QD BI 201335 combined with 600 mg TID BI 207127 for 28 weeks (no RBV)
The interim results will provide early virological response rates for all treatment arms of the novel interferon-free combination of BI 201335/BI 207127/ribavirin and are due to be presented by 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.

SILEN-C1
In SILEN-C1, 429 treatment-naïve patients with chronic genotype-1 HCV infections were randomised to the following treatment groups:
• Placebo
• BI 201335 120 mg QD with 3 days lead-in (LI) of PegIFN/RBV
• BI 201335 240 mg QD/LI
• BI 201335 240 mg QD without LI
In each arm, BI 201335 or placebo were given for 24 weeks together with PegIFN/RBV for 24 or 48 weeks. Results presented at AASLD will include an analysis of sustained virological response across different baseline factors, including difficult to treat HCV cases.

SILEN-C3
In SILEN-C3, 159 treatment-naïve genotype-1 patients were randomised to the following treatment groups:
• BI 201335 120mg QD for 12 weeks with 3 days lead-in of PegIFN/RBV
• BI 201335 120mg QD for 24 weeks with 3 days lead-in of PegIFN/RBV
In each arm, PegIFN/RBV was given for 24 or 48 weeks. Results presented at AASLD will provide an analysis of 12 versus 24 weeks of treatment with BI 201335.
Titles for accepted abstracts are below and full results and conclusions for these abstracts will be shared at AASLD at the times specified.
• Virologic response to an interferon-free regimen of BI 201335 and BI 207127, with and without ribavirin, in treatment-naïve patients with chronic genotype-1 HCV infection: Week 12 interim results of the SOUND-C2 study
(Poster LB-15. Zeuzem, et al. November 7, 8:00 a.m. - 5:30 p.m. PT)

Oral presentations
• SILEN-C3: Treatment for 12 or 24 weeks with BI 201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naïve patients with chronic genotype-1 HCV infection
(Abstract 39. D. Dieterich, et al. November 6, 4:15 p.m. - 4:30 p.m. PT)
• Treatment with the second generation HCV protease inhibitor BI 201335 results in high and consistent SVR rates - results from SILEN-C1 in treatment-naïve patients across different baseline factors
(Abstract 226. M.S. Sulkowski, et al. November 8, 8:45 a.m. - 9:00 a.m. PT)
• High sustained virologic response following interferon-free treatment of chronic HCV GT1 infection for 4 weeks with HCV protease inhibitor BI 201335, polymerase inhibitor BI 207127 and ribavirin, followed by BI 201335 and PegIFN/ribavirin - the SOUND-C1 study
(Abstract 249. S. Zeuzem, et al. November 8, 11:15 a.m. - 11:30 a.m. PT)

Poster presentation
• Characterization of HCV NS3 variants that emerged during virologic breakthrough and relapse from BI 201335 phase 2 SILEN-C1 study
(Poster 1339. G. Kukolj, et al., November 7, 8:00 a.m. - 5:30 p.m. PT)
The results from the HCV portfolio at AASLD underscore the promise of the company's pipeline as Boehringer Ingelheim continues to focus on the real-world challenges faced by HCV patients globally.
Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines for HCV patients. BI 201335 and BI 207127 are being investigated with the goal of improving cure rates for more HCV patients, including those traditionally difficult to treat.

Boehringer Ingelheim to show final Phase IIb data for it's BI 20133 protease inhibitor...

New data from the Boehringer Ingelheim hepatitis C virus (HCV) portfolio will be presented in oral scientific sessions at the International Liver CongressTM 2011, the 46th Annual Meeting of the European Association for the Study of the Liver (EASL), taking place 30 March-3 April in Berlin, Germany. The data will include final results from SILEN-C1 and SILEN-C2, two Phase IIb studies evaluating one of Boehringer Ingelheim’s investigational compounds for Hepatitis C treatment, the once-daily, oral protease inhibitor BI 201335 in combination with the current standard-of-care (pegylated-interferon and ribavirin).

Oral presentations (Friday, 1 April, 2011; Parallel Session: HCV Drug Development, Hall 1)

SILEN-C1: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naïve patients with chronic genotype 1 HCV infection
(Abstract 60. M. Sulkowski, et al. 16:00h - 16:15h)

SILEN-C2: Sustained Virologic Response (SVR) and safety of BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in chronic HCV genotype-1 patients with non-response to P/R
(Abstract 66. M. Sulkowski, et al. 17:30h - 17:45h)

Boehringer Ingelheim is continuing its long heritage in virology and is dedicated to developing new medicines to improve treatment for HCV patients. BI 201335 is part of a growing HCV portfolio that is being investigated with the aim of identifying a simpler HCV cure, overcoming the challenges of current treatments.

Additional HCV studies to be presented at EASL

SVR and Pharmacokinetics of the HCV protease inhibitor BI201335 with PegIFN/RBV in HCV genotype-1 patients with compensated liver cirrhosis and non-response to previous PegIFN/RBV
(Poster 1231. S. Pol, et al.; Saturday, 2 April, 2011, 09:00h - 18:00h)

Mechanisms of isolated unconjugated hyperbilirubinemia induced by the HCV NS3/4A protease inhibitor BI201335 (Poster 1236. R. Sane, et al.;Saturday, 2 April, 2011, 09:00h - 18:00h)
BI201335 Pharmacokinetics and early effect on viral load in HCV genotype-1 patients
(Poster 1249. C. Yong, et al.;Saturday, April 2, 2011, 09:00h - 18:00h)

Preclinical Characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BILB 1941 (Poster 1215. G. Kukolj et. al.; Friday, 30 March, 2011, 09:00h - 18:00h)
The abstracts can be accessed through the EASL website, www.easl.eu.

For more information on BI’s hepatitis portfolio, please visit www.boehringer-ingelheim.com and follow us on Twitter. www.twitter.com/boehringer.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 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.

Within the company’s global research network, Virology is one of the seven R&D areas with focus on Hepatitis C.

In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro (US $17.7 billion) while spending 21% of net sales in its largest business segment, Prescription Medicines, on research and development.

Boehringer Ingelheim starts STAT-C combination study...

According to Clinical Trails.gov, Boehringer Ingelheim has initiated a STAT-C combination study looking at their compounds BI 207127 (Non-nucleoside polymerase inhibitor) and BI 201335 (Protease inhibitor) plus Ribavirin. This study does not have an interferon component.

They are recruiting 302 naive patients who will be randomized to the following arms:
4 weeks of high dose TID BI 207127 + QD BI 201335 (protease inhibitor) + RBV
4 weeks of low dose TID BI 207127 and QD BI 201335 + RBV
24 or 48 weeks of high dose TID BI 207127 and QD BI 201335 + RBV
24 or 48 weeks of high dose BID BI 207127 and QD BI 201335 + RBV
24 or 48 weeks of high dose TID BI 207127 and QD BI 201335

The primary outcome measures are RVR and SVR. All sites are in the EU

http://clinicaltrials.gov/ct2/show/NCT01132313?term=hepatitis+OR+hep+OR+HCV&lup_s=05%2F01%2F2010&lup_d=30