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Boehringer Ingelheim's faldaprevir (BI201335), up to 85% SVR in treatment naive

Nov 11, 2012 - 0 comments
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Boehringer Ingelheim (BI) announced that faldaprevir (BI201335) and BI207127 combined with Ribavirin showed up to 85% SVR in treatment naive Hep C patients and up to 69% SVR in G1a and 1b patients, including some with advanced liver disease.  According to BI, subtype, genome type, and gender proved to be significant predictors for success.  Results are being presented at the AASLD conference in Boston Nov, 2012.  BI will also begin Phase 3 trials that will include Cirrhotics soon.
Faldaprevir (BI201335) is a direct acting antiviral small molecule protease inhibitor.
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AASLD- BI 201335 and BI 207127: Interferon-Free Hepatitis C Treatment Show Viral Cure Achieved in Up to 85% Of Treatment-Naive

Phase 2b Data of Boehringer Ingelheim's Interferon-Free Hepatitis C Treatment Show Viral Cure Achieved in Up to 85% of Treatment-Naive Patients

Results to be presented at American Association for the Study of Liver Diseases (AASLD) Annual Meeting, Phase 3 IFN-free trial program now being initiated..

By Boehringer Ingelheim Pharmaceuticals, Inc.

Published: Saturday, Nov. 10, 2012 - 7:07 am
BOSTON and RIDGEFIELD, Conn., Nov. 10, 2012 -- /PRNewswire/ -- Final Phase 2b data from Boehringer Ingelheim's interferon (IFN)-free Phase 2b SOUND-C2 study showed that up to 85 percent of genotype 1b (GT1b) hepatitis C (HCV) patients achieved sustained virologic response (SVR or viral cure) 12 and 24 weeks after the end of treatment with the investigational treatment regimen of faldaprevir (BI 201335) and BI 207127, in combination with ribavirin (RBV). A viral cure was achieved for 69 percent of all patients included in the study (both GT1a and GT1b HCV infections), and includes patients with advanced liver disease that are more challenging to cure.
Pivotal Phase 3 trials evaluating an IFN-free regimen of faldaprevir, BI 207127 and ribavirin are now being initiated.

"Final results from this Phase 2b study show potential for an interferon-free HCV cure for patients with chronic HCV that historically have been among the most difficult to cure," said Stefan Zeuzem, M.D., Chief of the Department of Medicine and Professor of Medicine at the Goethe University Hospital in Frankfurt, Germany, and lead investigator of the study. "The SOUND-C2 trial provides valuable information regarding the types of patients that are more likely to respond to treatment with faldaprevir and BI 207127, which may be useful for attaining optimal antiviral outcomes in the clinical setting."

Comprehensive results from SOUND-C2 will be presented at the 63rd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in Boston, MA.
• An oral presentation of final results from the SOUND-C2 study, including an analysis of predictors of treatment response, will be presented on Tuesday, November 13 (ID# 232)
• An oral presentation of results from a sub-analysis of patients with compensated liver cirrhosis from the SOUND-C2 study will be presented on Sunday, November 11 (ID# 84)
• A poster presentation of a comparison of SVR4, SVR12 and SVR24 results from SOUND-C2 will be presented on Sunday, November 11 (ID# 778)

The SOUND-C2 study, which includes compounds each of which targets HCV in a different way (polymodal therapy*), is the largest Phase 2 IFN-free HCV trial to date, enrolling 362 HCV GT1 patients, the most difficult genotype to treat successfully and the most common genotype found in the US. Nine percent of patients in the SOUND-C2 study had compensated liver cirrhosis due to HCV (damaged or scarred liver tissue). As part of the study, investigators performed a detailed analysis of patient and virus characteristics to explore the likelihood of a patient's response to treatment with faldaprevir and BI 207127 in combination with RBV (regression analysis). HCV GT1 subtype, patient IL-28b genome type and patient gender were identified as significant predictors of treatment success.

*Polymodal therapy involves treatment that combines compounds that each work with different modes of action to inhibit viral replication, as seen with faldaprevir + BI 207127 + ribavirin.

"We are looking forward to continuing development of our HCVerso™ program and are now initiating Phase 3 clinical trials investigating interferon-free HCV treatment with faldaprevir and BI 207127," said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Through HCVerso™ Boehringer Ingelheim is striving to deliver new solutions that consider real-world challenges faced by patients and clinicians."

Final Results from SOUND-C2 and Predictors of Response
SOUND-C2 was an open-label, randomized, Phase 2b study that enrolled 362 treatment-naive HCV GT1 patients into five different treatment arms evaluating polymodal, IFN-free HCV treatment with Boehringer Ingelheim's investigational compounds faldaprevir and BI 207127, with and without RBV, for up to 40 weeks.

SOUND-C2 Trial Design and Results – SVR12 and 24
SVR
Group
Faldaprevir BI 207127 RBV Duration (wks) All Patients GT1a GT1b
A
N=81 120 mg QD 600 mg TID Y 16 48 (59%) 13/34 (38%) 35/47 (75%)
B
N=80 120 mg QD 600 mg TID Y 28 47 (59%) 14/32 (44%) 33/48 (69%)
C
N=77 120 mg QD 600 mg TID Y 40 40 (52%) 16/34 (47%) 24/43 (56%)
D
N=78 120 mg QD 600 mg BID Y 28 54 (69%) 13/30 (43%) 41/48 (85%)
E
N=46 120 mg QD 600 mg TID N 28 18 (39%) 2/18 (11%) 16/28 (57%)

In SOUND-C2, regression analysis identified HCV GT1 subtype, patient IL-28b genome type and gender as significant predictors of treatment response. Patients with GT1b were shown to be six times more likely to achieve SVR as compared to patients with HCV GT1a (95 percent CI; p<0.0001). Patients with the CC subtype of the IL-28b genome were more than four times as likely to achieve SVR compared to the CT and TT subtype of the genome.

The most common adverse events (AEs) in SOUND-C2 were skin changes (photosensitivity, rash), gastrointestinal (GI) disorders (vomiting, diarrhea), and jaundice due to transient benign bilirubin elevation (unconjugated hyperbilirubinemia). Treatment discontinuation due to AEs correlated with increased treatment duration, with discontinuations ranging from 4.9 percent in Arm A (16 weeks) to 24.7 percent in Arm C (40 weeks), which was the longest treatment duration evaluation in the study.

Results from SOUND-C2 Sub-analysis of Patients with Compensated Liver Cirrhosis due to HCV

Data from the SOUND-C2 study are the first data for an IFN-free regimen in HCV patients with compensated liver cirrhosis. This sub-analysis included 33 patients (nine percent of the study population) with compensated liver cirrhosis, as confirmed by either biopsy or Fibroscan. Investigators noted that data from this analysis support the continued development of this investigational IFN-free treatment regimen in Phase 3 trials for patients with compensated liver cirrhosis.

SOUND-C2 Sub-Analysis in Patients with Compensated Liver Cirrhosis
1335QD/7127TID/RBV
16, 28 or 40 weeks
Pooled (n=21) 1335QD/7127BID/RBV
28 weeks (n=9) 1335QD/7127TID 28 weeks (n=3)
GT1a
(n=7) GT1b
(n=14) GT1a
(n=4) GT1b
(n=5) GT1a
(n=0) GT1b
(n=3)
SVR12 / 24, n (%) 3 (43%) 8 (57%) 2 (50%) 4 (80%) N/A 1 (33%)
DCs due to AEs, n (%) 6* (29%) 1 (11%) 0
DCs due to rash, n (%) 3* (14%) 0 0
DCs due to photosensitivity, n (%) 2 (10%) 0 0
DCs due to vomiting, n (%) 1 (5%) 0 0
*No cases of erythema multiforme, Stevens-Johnson Syndrome (SJS), toxic epidermal necrosis, or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Comparison of SVR4, SVR12 and SVR24 Results from SOUND-C2

A comparison of results from the SOUND-C2 study shows that almost all patients (98 percent) in the study who achieved SVR4 continued to maintain undetectable virus levels and achieve SVR24. All of the patients who achieved SVR12 in the SOUND-C2 study maintained their undetectable virus levels and achieved SVR24.

Of the patients with undetectable hepatitis C virus levels at the end of treatment (EOT), and who received the treatment per the pre-specified protocol, 15 experienced documented relapse (7 percent). Relapse occurred within 12 weeks post-treatment for 14/15 patients. One patient in the 16 week study arm relapsed between 24-48 weeks post-treatment.

It should be noted that rare late relapses have been observed following both IFN-based and IFN-free treatment. It is unclear why these patients relapsed so late in the follow up period. These results emphasize the importance of monitoring patients for at least one year following the end of treatment regardless of whether they were treated with an IFN-based or IFN-free regimen.

Pivotal Phase 3 Program Now Beginning

Based on the results of SOUND-C2, Boehringer Ingelheim is now initiating a pivotal Phase 3 program. Three clinical trials will enroll approximately 1,200 treatment-naive HCV patients, including patients with compensated cirrhosis and those who are ineligible for IFN treatment.

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.

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

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.



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