SAN FRANCISCO & INGELHEIM, Germany - Wednesday, November 9th 2011 [ME NewsWire]
Data from SILEN-C1 and SILEN-C3 trial presented at AASLD
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Boehringer Ingelheimtoday announced results from two PhaseIIb studies evaluating the combination of the company’s next generation protease inhibitor, BI 201335, with pegylated interferon (PegIFN) and ribavirin (RBV) in treatment-naϊve genotype-1 (GT1) hepatitis C (HCV) patients.1,2 These data were presented in oral sessions at the American Association for the Study of Liver Diseases (AASLD) 2011 Liver Meeting in San Francisco, USA.
Data from the SILEN-C3 study showed the potential for BI 201335 to shorten patients’treatment duration to 12 weeks and improve the likelihood of viral cure (sustained viral response; SVR) compared to the former traditional standard of care -48 weeks of treatment with PegIFN/RBV alone.1,3 Furthermore, the SILEN-C1 study demonstrated the ability for BI 201335 to improve SVR in traditionally difficult to treat populations.4,5
“Reducing the length of treatment time for HCV patients is one of several important goals for Boehringer Ingelheim as we seek to innovate a better cure for this chronic disease. The SILEN-C3 study results are very encouraging and suggest that treatment with BI 201335 may not be required beyond 12 weeks in the majority of treatment-naϊve HCV patients,”1said Professor Klaus Dugi, Corporate Senior Vice President Medicine at Boehringer Ingelheim. “Results from the SILEN-C1 study in difficult to treat virus types are also encouraging and we are keen to see the outcomes of our BI 201335 Phase III studies in 2013.”2-5
The results from SILEN-C3 indicate that among patients achieving an extended rapid viral response (eRVR), 12 weeks of treatment with BI 201335 was sufficient to achieve SVR. Patients with undetectable HCV RNA in the blood prior to week 12 had similar SVR rates, whether they were treated for 12 or 24 weeks with BI 201335 (82% and 81%, respectively).1
In addition to the SILEN-C3 study, the overall analysis of the SILEN-C1 study shows that 83.1% of patients treated with BI201335 240 mg QD achieved SVR, compared with 56.3% of patients on PegIFN/RBV alone (p<0.0001). The majority of patients with difficult to treat HCV subtypes, such as patients with the viral GT1a or the IL-28B non-CC gene variant (polymorphism), achieved SVR:
Specifically, among patients with GT1a HCV (n=32), a virus type that is more likely to resist treatment than GT1b, 82% achieved SVR, while for GT1b HCV patients (n=38), 84% achieved SVR
In addition, SVR was 71% for patients with the non-CC polymorphism of the IL-28B gene (n=29). While patients with the CC polymorphism (n=11) achieved 100% SVR and those where IL-28B genotyping was missing (n=31) achieved 86% SVR. Patients exhibiting the non-CC polymorphism are less likely to achieve SVR with PegIFN/RBV treatment2
GT1 HCV is the most challenging genotype of HCV to treat3 and those carrying the IL-28B non-CC polymorphism are less likely to achieve SVR than those with the CC polymorphism, with some studies showing an almost seven fold difference in treatment response.6
Study details:
(Oral presentation at AASLD: November 6, 4:15 p.m. -4.30p.m. PT, Abstract 39) SILEN-C3: Treatment for 12 or 24 weeks with BI 201335 combined with peginterferon alfa-2a and ribavirin (P/R) in treatment-naϊve patients with chronic genotype-1 HCV infection1
In this open-label PhaseII trial, 159 treatment-naϊve GT1 HCV patients were randomised to receive 120 mg QD BI 201335 for 12 or 24 weeks, each after three days lead-in (LI) with pegylated interferon and ribavirin (PegIFN/RBV). In both groups, PegIFN/RBV was given for 24 weeks. Patients who did not achieve an eRVR, continued PegIFN/RBV to week 48. eRVR was defined as viral load less than 25 IU/mL at week 4 and undetectable at weeks 8-18.1
(Oral presentation at AASLD: November 8, 8:45 a.m. -9.00 a.m. PT, Abstract 226) Treatment with the 2nd generation HCV protease inhibitor BI 201335 results in high and consistent SVR rates -results from SILEN-C1 in treatment-naϊve patients across different baseline factors2
SILEN-C1 is a double-blind, randomised, placebo-controlled trial, that randomised 429 treatment-naϊve GT1 HCV patients (1:1:2:2) to receive either placebo or BI 201335 120 mg with three days Lead-in (LI) of PegIFN/RBV, BI 201335 240 mg QD with three days LI or BI 201335 mg 240mg QD without LI. In each treatment group, BI 201335 was given for 24 weeks together with PegIFN/RBV for 24 or 48 weeks. This presented analysis of SILEN-C1 evaluated SVR according to various baseline characteristics. SVR results from all SILEN-C1 study groups were previously presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) in April 2011.2
NOTES TO EDITORS
Other BI data presented at the meeting include:
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)
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)
Virologic response to an interferon-free regimen of BI 201335 and BI 207127, with and without ribavirin, in treatment-naϊve patients with chronic genotype-1 HCV infection: week 12 interim results of the SOUND-C2 study (Poster LB-15. S. Zeuzem, et al. November 7, 8:00 a.m. - 5:30 p.m. PT)
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 170 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.
Glossary of HCV terms Sustained virologic response (SVR) is the goal of HCV treatment. SVR is measured 24 weeks following the conclusion of HCV treatment. If the virus remains undetectable at this time, a patient has achieved SVR and is considered cured of their HCV.
SVR12 is a measurement taken 12 weeks following the conclusion of treatment, If the virus remains undetectable at this time, a patient has achieved SVR12. This is considered highly predictive of cure or SVR. In fact, the US Food and Drug Administration has announced that it will now review HCV treatments based on clinical trial data through SVR12 to allow potential new HCV treatments to be filed before SVR is measured.
Ribonucleic acid (RNA) is one of the two types of nucleic acids found in all cells of the body, and is also part of the genetic material for hepatitis C virus. Often referred to as ‘viral load”, the amount of HCV RNA present in the blood is an important measurement for confirming the diagnosis and guiding the treatment of HCV infection.
Rapid virologic response (RVR) is defined as undetectable HCV RNA at week 4 of treatment. It provides an indication of how the patient will respond to treatment. Patients are more likely to achieve SVR if they have had a RVR.
Extended rapid virologic response (eRVR) is a rapid virologic response that endures through week 12 of treatment. Patients achieving an eRVR are very likely to ultimately achieve SVR and be cured of their HCV infection.
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.
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References 1. 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-naϊve patients with chronic genotype-1 HCV infection.
2. 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-naϊve patients across different baseline factors.
3. 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.
4. Soriano, Vicent et al. Directly acting antivirals against hepatitis C virus. Journal of Antimicrobial Chemotherapy. 2011; 66: 1673-1686.
5. National Institutes of Health Consensus Development Program: Management of Hepatitis C, 2002. http://consensus.nih.gov/2002/2002Hepatitisc2002116html.htm.
6. British HIV Association: Gene variant that helps hepatitis C treatment may hinder HIV treatment, 2011. http://www.bhiva.org/News.aspx?NewsID=a7503829-94b9-4d2f-bd91-1d2fbaad6e8d.
Contacts
Boehringer Ingelheim GmbH
Julia Meyer-Kleinmann
Director Corporate Communications
Phone: + 49 - 6132 -77 8271
E-mail: press@boehringer-ingelheim.com
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