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Positive Interim Results from Interferon-Free Phase 2b SOUND-C2 Study with Boehringer Ingelheim's Two Investigational HCV Direct Acting Antivirals Presented at AASLD - press release
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Planned interim analysis shows up to 76 percent of patients achieved a viral response through 12 weeks of treatment with BI 201335 plus BI 207127 and ribavirin
San Francisco, CA and Ridgefield, CT, November 7, 2011 - Boehringer Ingelheim Pharmaceuticals, Inc. today announced results from a planned interim analysis of a Phase 2b study, SOUND-C2, that showed the combination of two oral direct acting hepatitis C virus (HCV) compounds - the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127 with ribavirin (RBV) - was successful in reducing viral load below the lower limit of quantifiable levels at week 12 (viral response) in the majority of treatment-naïve patients infected with chronic genotype-1 (GT1) HCV. None of the five study arms included treatment with interferon. These data were presented as a late-breaking poster at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, CA.
"Results from the planned interim analysis of SOUND-C2 are encouraging," 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. "They show that BI 201335 plus BI 207127 with ribavirin suppressed the hepatitis C virus to undetectable levels in the majority of patients in this study. We must now complete the study to confirm if this interferon-free regimen leads to a sustained viral response."
"BI is developing our dual oral direct acting antiviral treatment regimen with the goal of eliminating interferon from HCV treatment. We are excited by these interim results and look forward to final study outcomes," said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "We also are pleased to present other data from our hepatitis C virus portfolio that underscores our ongoing focus on real-world challenges faced by HCV patients, including traditionally difficult-to-treat populations."
The interferon-free oral combination therapy arms with BI 201335, BI 207127 and RBV showed high virologic response rates through week 12 across treatment arms. Viral suppression also was observed in the RBV-sparing arm but was lower than in the other arms at week 12.
· 76 percent of patients who received BI 201335 once daily (QD) plus BI 207127 twice daily (BID) with RBV achieved viral response through week 12.
· 70 percent of patients who received BI 201335 QD plus BI 207127 three times daily (TID) with RBV achieved viral response through week 12.
· 57 percent of patients who received BI 201335 QD plus BI 207127 TID without RBV achieved viral response through week 12.
Breakthrough occurred in 13 percent of patients in BI 201335 plus BI 207127 TID with RBV treatment groups (arms one - three) and in 21 percent of patients in the BI 201335 plus BI 207127 BID with RBV treatment group. Breakthrough occurred in 15 percent of patients in the group that did not receive RBV.
The most frequent adverse events (AEs) were asthenia, pruritus, rash, photosensitivity, jaundice, nausea, vomiting and diarrhea. Across all treatment groups, 6-12 percent of patients discontinued due to AEs.
Results from this open-label, randomized, Phase 2b study were presented as a late-breaking poster titled, "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," by Stefan Zeuzem. In the study, 362 treatment-naïve GT1 HCV patients were randomized to receive either:
· BI 201335 120 mg QD plus BI 207127 600 mg TID plus RBV for 16 weeks;
· BI 201335 120 mg QD plus BI 207127 600 mg TID plus RBV for 28 weeks;
· BI 201335 120 mg QD plus BI 207127 600 mg TID plus RBV for 40 weeks;
· BI 201335 120 mg QD plus BI 207127 600 mg BID plus RBV for 28 weeks; or
· BI 201335 120 mg QD plus BI 207127 600 mg TID without RBV for 28 weeks.
Other BI data being presented at the meeting include:
· 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 36. D. Dieterich, et al. November 6, 4:15 p.m. - 4:30 p.m. PT)
· 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. - 5:00 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 Four 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)
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07 November 2011
Hepatitis C: Interferon-free combination of BI 201335 plus BI 207127 and ribavirin shows up to 76% of patients achieve a virological response at week 12, and 59% achieve SVR12 with 16 weeks treatment
Data from pre-specified interim analysis of Phase IIb SOUND-C21 trial with Boehringer Ingelheim's two investigational HCV direct-acting antivirals presented at AASLD
For media outside of the U.S.A. only
San Francisco, USA and Ingelheim, Germany [7 November 2011] - Boehringer Ingelheim today announced results from a pre-specified interim analysis of a Phase IIb study, named SOUND-C2. These data showed the combination of two oral direct acting anti hepatitis C virus (HCV) compounds (the protease inhibitor BI 201335 and the polymerase inhibitor BI 207127, with and without ribavirin (RBV), was successful in providing virological response rates at week 12 in treatment-naïve patients infected with the most difficult to treat genotype-1 (GT1) HCV. 1 The shortest treatment duration tested in the study (16 weeks) achieved SVR12 in 59% of patients. None of the five study arms included treatment with interferon. 1,2 These data were presented today at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, USA. 1
"Results from the interim analysis of SOUND-C2 look promising," 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. "They highlight the potential of BI 201335 plus BI 207127 to lessen the burden of existing treatments for a large portion of patients by offering a potential treatment option without the inclusion of interferon."
The use of interferon in HCV treatment is challenging for a number of patients due to suboptimal response rates, contraindications or severe side effects and treatment durations. 3
"We very much look forward to the final results from the SOUND-C2 study. The development of an oral interferon-free direct-acting antiviral regimen underlines Boehringer Ingelheim's goal of eliminating interferon from HCV treatment and a commitment to deliver innovative novel treatments in virology," said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. "At AASLD we will also present further data from anti-HCV portfolio that demonstrates our dedication to meet the real-world challenges of HCV patients globally, 1,4-7 including patient populations with traditionally difficult to treat virus types." 8-10
All five treatment arms of the interferon-free oral combination therapy of BI 201335/BI 207127/RBV showed high virologic response rates through week 12, defined by measuring the level of HCV RNA in patient blood:
· 70-76% of patients who received BI 201335 once daily (QD) + BI 207127 three times daily (TID) or twice daily (BID) with RBV achieved undetectable HCV RNA at week 12, with 13-21% of patients developing a viral load breakthrough during treatment
· 57% of patients who received BI 201335 QD + BI 207127 TID without RBV achieved viral response at week 12
· SVR12, which is considered highly predictive of SVR and cure of the infection, was achieved after 16 weeks of treatment in 59% of patients.
The safety and tolerability profile was comparable to other direct acting antiviral regimens.
Other BI data being presented at the meeting include:
· SILEN C3: Treatment for 12 or 24 weeks with BI201335 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) 4
· 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. - 5:00 p.m. PT) 5
· Treatment with the 2nd generation HCV protease inhibitor BI201335 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) 6
· High sustained virologic response following interferon-free treatment of chronic HCV GT1 infection for 4 weeks with HCV protease inhibitor BI201335, polymerase inhibitor BI207127 and ribavirin, followed by BI201335 and PegIFN/ribavirin -the SOUND-C1 study
(Abstract 249. S. Zeuzem, et al., November 8, 11:15 a.m. - 11:30 a.m. PT) 7
NOTES TO EDITORS
Results of this open-label, randomised, Phase IIb study were presented as a late breaking poster titled, "Virologic response to an interferon-free regimen of BI201335 and BI207127, with and without ribavirin, in treatment-naive patients with chronic genotype-1 HCV infection: Week 12 interim results of the SOUND-C2 study," by Professor Stefan Zeuzem. In the study, 362 treatment-naïve GT1 HCV patients were randomised into five interferon-free treatment groups, each with 120mg BI 201335 once daily but with different dosing of BI 207127 and treatment durations as follows:
· BI 201335 120mg QD + BI 207127 600mg 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 + RBV for 28 weeks; or
· BI 201335 120mg QD + BI 207127 600mg TID without RBV for 28 weeks.
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. The number of individuals chronically infected with HCV globally has been estimated at 175 million, with 3-4 million new infections occurring each year. Only about 20-45% of patients clear the virus in the acute phase. Of the remaining chronically infected patients, 20% will develop cirrhosis within a mean of 20 years. The mortality rate after cirrhosis has developed is 2-5% 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 its ongoing research program for HCV, Boehringer Ingelheim has a longstanding history in virology drug development, including compounds for the treatment of HIV (VIRAMUNE® (nevirapine) tablets/oral suspension, the first approved HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) and Aptivus®, an 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.
Boehringer Ingelheim in Hepatitis C Virus (HCV)
Boehringer Ingelheim has a dedicated HCV treatment development programme, called HCVersoTM, which at its core, aims to reverse the existing HCV paradigm. The ultimate aim of this programme is to deliver improved HCV treatment outcomes for patients whilst breaking down the barriers of current treatment regimens.
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 IIb (SILEN-C studies). This Phase II programme supports the investigation of BI 201335 in Phase III trials currently ongoing. Boehringer Ingelheim is also developing BI 207127, an NS5B RNA-dependent polymerase inhibitor that has completed Phase I clinical trials. Phase II trials evaluating BI 207127 with BI 201335 in interferon-sparing regimens, both with and without ribavirin, are currently underway.
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. 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.
In 2010, Boehringer Ingelheim posted net sales of about 12.6 billion euro while spending almost 24% of net sales in its largest business segment Prescription Medicines on research and development.
SVR = sustained viral response, referred to as HCV cure. SVR12 = sustained viral response at week 12 after treatment is completed. RVR = Rapid virologic response, undetectable viral RNA at week 4 of treatment (indicator of how patient will respond). eRVR = extended rapid virologic response, undetectable viral RNA enduring through week 12 of treatment.
REFERENCES
1. Zeuzem, Stefan, et al. Virologic response to an interferon-free regimen of BI201335 and BI207127, with and without ribavirin, in treatment-naive patients with chronic genotype-1 HCV infection: Week 12 interim results of the SOUND-C2 study.
2. Mensa, Federico J. BI 207127 - BI 201335 (O2) program Overview; IFN-sparing oral regimen. Barcelona, May 19, 2011.
3. http://www.thebody.com/content/art12308.html (last accessed 4th March 2011)
4. Dieterich, Douglas et al. SILEN-C3: Treatment for 12 or 24 weeks with BI201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naïve patients with chronic genotype-1 HCV infection.
5. Kukolj, G. et al. Characterization of HCV NS3 variants that emerged during virologic breakthrough and relapse from BI 201335 phase 2 SILEN-C1 study.
6. Sulkowski, Mark et al. Treatment with the 2nd generation HCV protease inhibitor BI201335 results in high and consistent SVR rates - results from SILEN-C1 in treatment-naïve patients across different baseline factors.
7. Zeuzem, Stefan et al. High sustained virologic response following interferon-free treatment of chronic HCV GT1 infection for 4 weeks with HCV protease inhibitor BI201335, polymerase inhibitor BI207127 and ribavirin, followed by BI201335 and PegIFN/ribavirin -the SOUND-C1 study.
8. Soriano, Vicent et al. Directly acting antivirals against hepatitis C virus. Journal of Antimicrobial Chemotherapy. 2011; 66: 1673-1686.
9. Ghany, Marc 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.
10. National Institutes of Health Consensus Development Program: Management of Hepatitis C, 2002. http://consensus.nih.gov/2002/2002Hepatitisc2002116html.htm.
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