Boehringer Ingelheim presents interferon-free SOUND-C2 data at EASL...

Today (Saturday, April 21, 2012) is the big day all us HCV drug development nerds (I'd use 'wonks', but that sounds even worse) are waiting for in regards to the late-breaker presentations from EASL and any additional nuggets of info.  One of those presentations will  on the SOUND-C2 trial, featuring the interferon-free combination of Boehringer Ingelheim's HCV PI BI 201335 and polymerase inhibitor BI 207127 both with  ribavirin. According to the press release below, the interim results of the combo show a 68% SVR12 overall in genotype 1 patients in the 28 week arm regardless of IL-28B status. In the 16 week arm, SVR12 was achieved in 59% of patients.  As one might suspect, those subjects that were genotype 1a and non-CC IL-28B status experienced higher relapse and breakthrough rates than those who were G1b and CC.  It was also found that without the benefit of ribavirin, the subjects did substantially worse with only at 39% SVR12.  


Details are still coming, but it appears that this will be a 28 week option and the G1a non-CC patients may either need to go longer (there is a 40 week arm of this study that awaits presentation) or the addition of interferon. Ribavirin will clearly be needed in this combination as well. The odds of dosing confusion are a bit higher, with the PI boasting QD dosing and the polymerase inhibitor BID dosing.


A sub-analysis looking at the efficacy of the combination in the compensated cirrhotic was also presented in poster format. Although the numbers are small and clearly the G1b subjects respond better to the combo, it's encouraging to see any sort of SVR12 in this extremely difficult to treat population, especially without the aid of interferon.

Phase 2b Study of Boehringer Ingelheim’s Interferon-Free Hepatitis C Treatment Shows Undetectable Virus in HCV Genotype-1 Patients 12 Weeks After Treatment Ended (SVR12)

Barcelona, Spain and Ridgefield, CT, April 19, 2012 – New data from a pre-specified interim analysis of the Phase 2b SOUND-C2 study show that 68 percent of genotype-1 (GT1) hepatitis C virus (HCV) patients achieved sustained viral response 12 weeks after the end of treatment (SVR12) with Boehringer Ingelheim’s investigational direct-acting antiviral compounds – the protease inhibitor BI 201335 and polymerase inhibitor BI 207127 – plus ribavirin (RBV), without interferon. SVR12 has been highly correlated with SVR24, which is a recognized indicator of viral cure. These patients received combination therapy with BI 201335 once-daily (QD), BI 207127 twice-daily (BID) and RBV for 28 weeks. The SOUND-C2 study investigated interferon-free treatment in HCV GT1 patients, the most difficult genotype to treat, regardless of IL-28B status. Among study participants, 10 percent had compensated liver cirrhosis.

“Eliminating interferon from HCV treatment is an urgent need,” 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. “The antiviral activity of BI's all oral direct-acting antiviral compounds in the SOUND-C2 study demonstrates the potential for an interferon-free cure for HCV.”

Furthermore, a separate arm of the SOUND-C2 study showed that after 16 weeks of interferon-free treatment, SVR12 was achieved in 59 percent of patients. Investigators presented relapse data broken out by genotype and IL-28B status. The rate of relapse in the treatment arms ranged between 2 and 10 percent for GT1b and GT1a-CC patients. There was a higher rate of relapse in GT1a non-CC patients, with relapse ranging from 0 to 40 percent. The full results from this interim analysis of SOUND-C2 are being presented on Saturday, April 21, at the International Liver Congress, the 47th Annual Meeting of the European Association of the Study of the Liver (EASL 2012) in Barcelona, Spain (Abstract #101). These results supplement the abstract findings highlighted today during an official EASL press conference.

“We are looking 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 Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “We are committed to the millions of people around the world who are chronically infected with HCV. Through our clinical trial program HCVersoTM, we are working with experts worldwide to ask the difficult questions that remain in HCV to find answers to the challenges that these patients face.”

Planning of the interferon-free Phase 3 clinical trial program is underway.

SOUND-C2 Pre-Specified Interim Analysis
In this open-label Phase 2b study, 362 treatment-naïve GT1 HCV patients were randomized into five interferon-free treatment groups, each with 120 mg BI 201335 QD, but with different dosing of BI 207127 and treatment durations. The randomization was stratified by HCV genotype (1a or 1b) and patient IL-28B genotype, with 41 percent of patients being GT1a and 75 percent being IL-28B CT or TT.

Investigators reported breakthrough broken out by genotype and IL-28B status. In GT1b and GT1a-CC patients, breakthrough occurred in 7 percent of patients in Arm A, 11 percent of patients in Arm B, 19 percent of patients in Arm C, 9 percent of patients in Arm D, and 29 percent of patients in Arm E (no RBV arm). In GT1a non-CC patients, breakthrough occurred in 40 percent of patients in Arm A, 50 percent of patients in Arm B, 25 percent of patients in Arm C, 64 percent of patients in Arm D, and 91 percent of patients in Arm E (no RBV arm).

In this study, the most common adverse events (AEs) were skin (photosensitivity, rash), gastrointestinal (GI) disorders (vomiting, diarrhea), and jaundice due to unconjugated hyperbilirubinemia. Treatment discontinuations due to AEs correlated with increased dosing frequency and treatment duration, with discontinuations ranging from 4.9 percent in Arm A (16 weeks) to 24.7 percent in Arm C (40 weeks). In the arm with BID dosing of BI 207127 (Arm D), discontinuations were 7.7 percent. BID dosing of BI 207127 is planned for Phase 3 investigation.

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 enrolls first patient in Phase 3 trial for BI 201335

Good news for BI as the first patient is enrolled in their phase 3 trials looking at HCV protease inhibitior BI 201335 in combinations with peg and riba. VERY nice to see that they will be looking at this compound in the HIV/HCV co-infected patient, an area that the first generation of protease inhibitors, Telaprevir and Boceprevir may be lacking in due to drug interaction and tolerability issues

Boehringer Ingelheim Announces Enrollment of First Patient in Phase 3 Trial for Lead Hepatitis C Compound

Development program has been granted FDA Fast Track designation

RIDGEFIELD, Conn., April 26, 2011 /PRNewswire/ -- Boehringer Ingelheim Pharmaceuticals, Inc. today announced that enrollment has commenced at North American sites in its pivotal Phase 3 clinical trial program for BI 201335, the Company's investigational, oral protease inhibitor for the treatment of chronic hepatitis C virus (HCV). Phase 3 trials have begun recruiting to evaluate BI 201335 plus standard-of-care (SOC) in both treatment-naive and -experienced patients with chronic genotype-1 HCV, the most challenging HCV genotype to treat.(1) Results from the Phase 3 studies are expected in the first half of 2013.

The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development program for BI 201335. Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious diseases and fill an unmet medical need. The purpose is to get important new drugs to patients earlier.(2)

"We are pleased to have begun enrolling patients at North American trial sites as we continue development of BI 201335," said Peter Piliero, M.D., executive director, Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We look forward to initiating additional trials later this year in more patient populations, including HCV-HIV coinfected patients, as we continue to advance our HCV portfolio."

BI 201335 U.S. Phase 3 Trials

There are currently three Phase 3 trials enrolling patients around the world that together seek to enroll approximately 1,875 patients. Two of the three trials have U.S. trial sites that together plan to enroll approximately 495 patients.

In the U.S., Study 1220.47 will enroll approximately 370 treatment-naive genotype-1 HCV patients at 95 trial sites. This study will also include additional sites in Canada, Taiwan and Korea. Study 1220.7 will enroll approximately 125 treatment-experienced genotype-1 HCV patients who have failed at least 12 weeks of prior treatment with SOC at 40 trial sites in the U.S. This study also includes additional trial sites around the world. In treatment-naive patients (Study 1220.47), BI 201335 will be dosed once-daily at either 120 mg or 240 mg for 12 or 24 weeks in combination with 24 or 48 weeks of pegylated interferon and ribavirin, the current HCV SOC. In treatment-experienced patients (Study 1220.7) BI 201335 will be dosed once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 48 weeks for prior partial and null responder patients. Patients with prior relapse will be dosed with BI 201335 once-daily at 240 mg for 12 or 24 weeks in combination with SOC for 24 or 48 weeks total duration. The primary endpoint of each trial is sustained viral response (SVR), which is considered viral cure.(3)

For more information about clinical trials involving BI 201335, please visit www.clinicaltrials.gov.

About Hepatitis C Virus (HCV)

HCV is an infectious disease of the liver and is a leading cause of chronic liver disease and liver transplant.(1,4) The number of individuals chronically infected with HCV globally has been estimated at 170 million, with three to four million new infections occurring each year.(5) Only about 20-45 percent of patients clear the virus in the acute phase.(5) Of the remaining chronically infected patients, 20 percent will develop cirrhosis within a mean of 20 years.(1) The mortality rate after cirrhosis has developed is two to five percent per year.(6) End-stage liver disease due to HCV infection currently represents the major cause for liver transplantation in the Western world.(1)

About Boehringer Ingelheim in Virology

Boehringer Ingelheim has more than 6,900 scientists working in cross disciplinary teams within our global R&D network in six large therapeutic areas, including virology. In addition to its ongoing research program for HCV, Boehringer Ingelheim has a long-standing history in virology drug development, including compounds for the treatment of HIV. The company has a well established research center in Laval, Canada, dedicated to virology research since the early 1990's, and is committed to developing new therapies for virologic diseases with a high unmet medical need.

Boehringer Ingelheim in Hepatitis C Virus (HCV)

BI 201335 is an investigational oral HCV NS3/4A protease inhibitor, discovered from Boehringer Ingelheim's own research and development, which has completed clinical trials through Phase 2b (SILEN-C studies). This Phase 2 program supports the investigation of BI 201335 in Phase 3 trials. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase 1 clinical trials. Phase 2 trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

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. 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 endeavors.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.

References:

National Digestive Disease Information Clearing House (NDDICH), NIH. Chronic Hepatitis C: Current Disease Management. http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm.
U.S. Food and Drug Administration (FDA). Fast Track Designation Request Performance. http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm122932.htm.
American Association for the Study of Liver Disease Practice Guidelines: Diagnosis, Management, and Treatment of Hepatitis C: An Update. Hepatology, April 2009. http://www.natap.org/2009/HCV/aasld.pdf.
Centers for Disease Control and Prevention (CDC). Hepatitis C FAQs for the Public. http://www.cdc.gov/hepatitis/C/cFAQ.htm.
World Health Organization (WHO): Europe. Hepatitis: Hepatitis C. http://www.euro.who.int/en/what-we-do/health-topics/diseases-and-conditions/hepatitis/facts-and-figures/hepatitis-c.
Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009. http://cid.oxfordjournals.org/content/48/3/313.full.



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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