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Nov 30, 2012

Nov 30, 2012 - 0 comments

Labs are good, CT scan is good, liver compensated, no ascites, no varices.

Hepatitis C Tracker

Bristol-Myers Squibb Co., Phase 2 Data, Asunaprevir & Daclatasvir, up to 78% SVR rate in G1b previous null responders

Nov 12, 2012 - 1 comments
Tags:

Asunaprevir

,

Daclatasvir

,

Hepatitis C



Bristol-Myers Squibb Company (BMS) announced yesterday at the Liver Meeting in Boston, Nov. 2012, that the dual regimen of the NS3 protease inhibitor asunaprevir (ASB) with the NS5A inhibitor daclatasvir (DCV)  without Interferon or Ribavirin showed up to 78% SVR12 rates in G1b's who were previously null responders.
Advocate1955
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AASLD-Daclatasvir and Asunaprevir Achieved SVR12 in 78% of Difficult-to-Treat Genotype 1b Prior Null Responders  

Investigational Hepatitis C Dual DAA Regimen of Daclatasvir and Asunaprevir Achieved SVR12 in 78% of Difficult-to-Treat Genotype 1b Prior Null Responders In Expanded Phase II Study            
• Interferon- and ribavirin-free dual DAA regimen is one of multiple daclatasvir-based regimens in development to help meet the needs of diverse HCV patient population
• Findings support both the global and Japanese daclatasvir registrational programs
Sunday, November 11, 2012 4:45 pm EST

BOSTON--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced new Phase II data demonstrating that the dual regimen of the investigational NS5A replication complex inhibitor daclatasvir (DCV) and the investigational NS3 protease inhibitor asunaprevir (ASV), without interferon or ribavirin, achieved high rates of sustained virologic response 12 weeks post-treatment (SVR12) in patients with genotype 1b (GT1b) hepatitis C virus (HCV) who were prior null responders to alfa interferon and ribavirin (alfa/RBV). In this study, the DCV/ASV Dual regimen achieved SVR12 in 78% (14/18) and 65% (13/20) of GT1b patients when asunaprevir was dosed twice daily (Group A1) or once daily (Group A2), respectively.
  
These results were presented today at the American Association for the Study of Liver Diseases congress in Boston, along with data from this same study on the safety and efficacy of quadruple therapy with DCV/ASV/alfa/RBV in predominantly GT1a prior null responders.
  
In the patients treated with the DCV/ASV Dual regimen therapy, there were no serious adverse events related to study drug or discontinuations due to adverse events. Overall, headache was the most common adverse event in the DCV/ASV Dual regimen groups (Group A1: 44%, Group A2: 40%).
  
“We continue to see a significant unmet need for treatment approaches that improve response rates in patients with hepatitis C genotype1b who have not responded to prior therapy, with currently available treatment regimens achieving low cure rates of 30 to 40%,” said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb. “The high response rates seen in this study with daclatasvir and asunaprevir are encouraging as we seek interferon- and ribavirin-free hepatitis C regimens for this difficult-to-treat patient population.”
  
Daclatasvir is the first NS5A replication complex inhibitor to be investigated in HCV clinical trials and is currently in Phase III development. Asunaprevir is an oral, NS3 protease inhibitor in Phase III development with daclatasvir. The DCV/ASV Dual regimen is part of a global registrational program and a registrational program specific to Japan, where the majority of HCV patients have GT1b.

Study Design and Results
The expansion of this randomized, open-label, phase IIa study evaluated the antiviral activity and safety of the combination of DCV and ASV with and without alfa/RBV in 101 HCV genotype 1 prior null responders to alfa/RBV. The primary endpoint of the study was the proportion of patients achieving undetectable viral load (HCV RNA < LLOQTND) 12 weeks post-treatment (SVR12).
Patients received one of five treatment regimens for 24 weeks. Genotype 1b infected patients were randomized to receive one of four treatment regimens for 24 weeks (two DCV/ASV Dual treatment groups, two DCV/ASV/Alfa/RBV Quad treatment groups). Genotype 1a infected patients were randomized to receive one of two treatment regimens for 24 weeks (two DCV/ASV/Alfa/RBV Quad treatment groups). A fifth group (DCV/ASV/RBV Triple therapy) included both GT1a and GT1b infected patients and enrolled separately. The DCV/ASV Dual treatment groups received DCV 60 mg once daily and ASV 200 mg either twice daily (Group A1) or once daily (Group A2).
  
Virologic Response
• In Group A1 (DCV + ASV 200 mg BID), 78% (14/18) of patients achieved SVR12. Of the four patients who did not achieve SVR12, one patient was missing a viral load measurement at 12 weeks post-treatment and one had transient viremia (detectable viral load). Both of these patients had undetectable viral load on subsequent visits.
• In Group A2 (DCV + ASV 200 mg QD), 65% (13/20) of patients achieved SVR12
• With DCV/ASV Dual therapy, eight total patients experienced virologic breakthrough1 – two Group A1 patients and six Group A2 patients. All received rescue therapy with the addition of alfa/RBV to their regimen. One Group A2 patient relapsed post-treatment at week 4.
• An analysis of HCV sequences confirmed that five of the six Group A2 patients with virologic breakthrough had baseline polymorphisms that confer DCV resistance (NS5A domain). Additionally, at breakthrough, seven patients had confirmed resistance to both DCV and ASV.
Safety

In the patients treated with DCV/ASV Dual therapy, there were no serious adverse events due to study drug, no deaths, and no treatment discontinuations due to adverse events (AEs). Most AEs were mild to moderate in severity. The most common AEs (≥40% in any group) were:

Adverse Event Group A1*
DCV + ASV 200 mg BID Group A2*
DCV + ASV 200 mg QD
Headache 44% (8/18) 40% (8/20)
Diarrhea 28% (5/18) 40% (8/20)
Weakness (asthenia) 28% (5/18) 30% (6/20)
Fatigue 28% (5/18) 10% (2/20)
Insomnia 22% (4/18) 15% (3/20)

* Adverse events in groups A1 and A2 includes patients who had alfa/RBV added to their regimen

Grade 3-4 AEs in Group A2 included neutropenia in one patient receiving alfa/RBV as rescue therapy. SAEs in Groups A1 and A2 included panic attack, forearm fracture, viral gastroenteritis, and prostate cancer; all were determined by study investigators to be unrelated to study therapy. Grade 3-4 ALT/AST elevations were infrequent and none were accompanied by elevated total or direct bilirubin. All AST/ALT elevations improved without intervention. All patients in groups A1/A2 with cytopenias were receiving alfa/RBV as rescue therapy.

About Bristol-Myers Squibb’s Commitment to Liver Disease
Bristol-Myers Squibb is studying a portfolio of compounds that aims to address unmet medical needs across the liver disease continuum, including hepatitis C, hepatitis B and liver cancer. The Company’s hepatitis C pipeline includes compounds with different mechanisms of action, pursuing both biologics as well as small molecule DAAs. These compounds are being studied as part of multiple treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies.
  
Daclatasvir is an NS5A replication complex inhibitor that is being extensively studied as a key component of potential DAA-based hepatitis C treatment regimens. Studied in more than 3,000 patients to date, daclatasvir is in Phase III development. Asunaprevir is an NS3 protease inhibitor in Phase III development for hepatitis C as a component of daclatasvir-based treatment regimens, and has been studied in more than 1,200 patients to date.

About Hepatitis C
Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C, with genotype 1 being the most prevalent genotype. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer.

About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement
This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995, regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compounds described in this release will support regulatory filings, or that the compounds will receive regulatory approvals or, if approved, they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb’s business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2011, in our Quarterly Reports on Form 10-Q, and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

1 Virologic breakthrough defined as ≥ 1 log increase from nadir in HCV RNA, HCV RNA ≥ LLOQ on or after Week 8, and confirmed HCV RNA < LLOQ-TD on or after Week 8 (DUAL and TRIPLE arms only)

Contact:
Bristol-Myers Squibb
Media:
Cristi Barnett, 609-252-6028
cristi.***@****


Abbott's triple DAA regimen plus Ribavirin, 12 weeks, high rates of SVR in both treatment naive and null responders

Nov 11, 2012 - 1 comments
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ABT triple DAA regimen

,

Hepatitis C



This information has already been posted on the Hep C forum, but I wanted to post it in my journals for future reference.  Abbott (ABT) will be presenting information at the AASLD meeting in Boston, Nov, 2012, regarding it's triple DAA regimen which produced high rates of SVR both in treatment naive and null responders both with and without Ribavirin, although results with Ribavirin are higher.  According to ABT's press release, the SVR rates after 12 weeks of treatment were:
GT1, treatment naive 97.5% SVR, null responders 93.3% SVR
GT1a, treatment naive 96% SVR, null responders 89% SVR
GT1b, treatment naive 100% SVR, null responders 100% SVR
ABT-450r is a protease inhibitor, ABT-333 is a polymerase inhibitor, and ABT-267 is a NS5A inhibitor.  Phase 3 will be enrolling.
Advocate1955
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Abbott Presents Promising Phase 2b Interferon-free Hepatitis C Results at 2012 Liver Meeting®

• Investigational Triple-DAA Regimen plus Ribavirin Treatment for 12 Weeks Demonstrated High SVR12 Rates in Intent-to-Treat Analysis
• Phase 3 Registrational Program Currently Enrolling

November 10, 2012
Abbott Park, Illinois (NYSE: ABT) — Results from Abbott’s phase 2b clinical trial, "Aviator," demonstrated high sustained viral response rates at 12 weeks post-treatment (SVR12) in all 8- and 12-week arms, with combinations of direct acting antivirals (DAAs) given with and without ribavirin (RBV). Results will be presented at the President's Press Conference and the latebreaking clinical trials session at the Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston.

Based on promising results from Aviator, Abbott has selected triple-DAA regimens, with and without ribavirin, to move forward into phase 3 clinical trials. Topline intent-to-treat results for the 12-week, triple-DAA regimen with ribavirin are as follows:

• SVR12 in treatment-naïve genotype 1 (GT1) patients was 97.5 percent (77 of 79), and 93.3 percent (42 of 45) in GT1 null responder patients
• In GT1a patients, SVR12 was achieved in 96 percent (52 of 54) of treatment naïve patients and 89 percent (25 of 28) of null responder patients
• In GT1b patients, SVR12 was achieved in 100 percent of treatment naïve (25 of 25) and null responder patients (17 of 17)

In addition, results from the 12-week triple-DAA regimen without RBV in treatment naïve patients showed:
• SVR12 was achieved in 87.3 percent (69 of 79) of GT1 patients
• SVR12 in GT1a patients was 83 percent (43 of 52)
• SVR12 in GT1b patients was 96 percent (24 of 25)

"Based on the high SVR12 results with Abbott’s triple-direct acting antiviral regimen in GT1 patients, it appears we are moving closer to potential oral treatment regimens that do not require interferon to treat HCV," said Kris Kowdley, M.D., director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center, and Clinical Professor of Medicine at the University of Washington in Seattle. "This is encouraging news for the many patients who are unable or unwilling to take interferon."

About Study M11-652 (Aviator)
This phase 2b study assesses the safety, and efficacy of ABT-450/r (dosed 100/100mg to 200/100mg QD), ABT-267 (25mg QD), ABT-333 (400mg BID) and ribavirin in non-cirrhotic treatment-naïve patients and prior peg-interferon/ribavirin null responders for 8, 12 or 24 weeks. Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based. Results from the treatment groups are summarized in the chart below.

Treatment-Naïve Null Responders
Duration 8 weeks 12 weeks 12 weeks
Regimen ABT-450/r
ABT-267
ABT-333
RBV ABT-450/r

ABT-333
RBV ABT-450/r
ABT-267
  
RBV ABT-450/r
ABT-267
ABT-333 ABT-450/r
ABT-267
ABT-333
RBV ABT-450/r
ABT-267

RBV ABT-450/r
ABT-267
ABT-333
RBV
Number dosed 80 41 79 79 79 45 45
Relapses 9 4 5 5 1 5 0
Breakthroughs 0 1 1 1 0 0 3
Lost to Follow up (LTFU) or withdrew consent 1 1 2 4 1 0 0
SVR12 (ITT)1 87.5%
(70/80) 85.4% (35/41) 89.9% (71/79) 87.3% (69/79) 97.5% (77/79) 88.9% (40/45) 93.3% (42/45)
SVR12 (OD)2 88.6% (70/79) 87.5% (35/40) 92.2% (71/77) 92% (69/75) 98.7% (77/78) 88.9% (40/45) 93.3% (42/45)
SVR12 (ITT) GT1a 84%
(47/56) 79%
(23/29) 85%
(44/52) 83%
(43/52) 96%
(52/54) 81%
(21/26) 89%
(25/28)
SVR12 (ITT) GT1b 96%
(23/24) 100%
(12/12) 100%
(27/27) 96%
(24/25) 100%
(25/25) 100%
(18/18) 100%
(17/17)

1. ITT (Intent-to-treat) population: includes all patients who received at least one dose of study drug
2. OD (Observed data): Excludes patients with values missing for reasons other than virologic failure or discontinuation due to AEs

"The 93.3 percent SVR12 seen with triple-DAA therapy with ribavirin in previous null responder patients in Aviator is noteworthy given the limited treatment options with interferon-based therapies for this patient population," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott. "As the data from the Aviator study have matured, we are encouraged that we have continued to see high SVR12 rates. Results from Aviator have allowed Abbott to confidently move into larger, confirmatory Phase 3 trials with the goal of being the first company to bring an interferon-free treatment regimen to genotype 1 patients."

Aviator Safety Results
Four of 448 patients (one percent) in the 8- and 12-week arms discontinued due to adverse events. Of five serious AEs (1 percent), one (arthralgia or joint pain) was possibly study drug-related. In the trial, the most common adverse events were fatigue (28 and 27 percent) and headache (28 and 31 percent) for treatment naïve and null responders respectively.

About the Hepatitis C Virus
Hepatitis C is a liver disease affecting as many as 170 million people worldwide. The virus is primarily spread through direct contact with the blood of an infected person. HCV increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death; and liver disease associated with HCV infection is growing rapidly.
Of the six main genotypes of hepatitis C, genotypes 1, 2 and 3 are the most widespread. Genotype 1 is the most common genotype in the U.S. and the most difficult to treat with interferon based therapies. Patients with genotypes 2 and 3 are more likely than individuals with genotype 1 to respond to therapy with peg-interferon or the combination of peg-interferon and ribavirin.

About Abbott's HCV Development Programs
Abbott's HCV portfolio includes investigational medicines with three different mechanisms of action, including protease (ABT-450/r), polymerase (ABT-333) and NS5A (ABT-267) inhibitors, currently being studied in clinical trials. ABT-450 is being developed with low dose ritonavir which enhances the pharmacokinetic properties of ABT-450. The use of ritonavir 100mg with ABT-450 for the treatment of HCV is investigational.
ABT-450 was discovered during the course of a collaboration between Abbott and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by Abbott for use in combination with Abbott's other investigational medicines for the treatment of HCV. Abbott is well-positioned to explore combinations and co-formulations of these medicines.
On Monday, November 12 at 5:30 p.m. EST, Abbott will host an investor webcast to discuss the phase 2b Aviator data, as well as our recently initiated phase 3 registrational program. The webcast can be accessed on Abbott’s investor relations website at abbottinvestor.com.

Ritonavir Use in Treatment of HIV
Ritonavir is in a class of medicines called the HIV protease inhibitors. Ritonavir is used in combination with other anti-HIV medicines to treat people with human immunodeficiency virus (HIV) infection. Ritonavir is for adults and for children greater than 1 month in age and older.

Ritonavir does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. People taking ritonavir may still get opportunistic infections or other conditions that happen with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium avium complex (MAC) infections.
Ritonavir Safety in Treatment of HIV

Patients should not take ritonavir with certain medicines, as these can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties, or excessive sleepiness. Patients should not take ritonavir if they have had a serious allergic reaction to any of its ingredients. Some patients taking ritonavir may develop liver and pancreas problems, which can cause death.

Patients may develop large increases in triglycerides and cholesterol, diabetes, high blood sugar, changes in body fat, increased bleeding in people with hemophilia, allergic reactions, and/or changes in heart rhythm. Patients may develop signs and symptoms of infections that they already have after starting anti-HIV medicines.
For more information, please see Important Safety Information and Full Prescribing Information.

About Abbott
Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacturing and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs approximately 91,000 people and markets its products in more than 130 countries.

http://abbott.com/news-media/press-releases/abbott-presents-promising-phase-2b-interferonfree-hepatitis-c-results-at-2012-liver-meeting.htm




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

Nov 11, 2012 - 0 comments
Tags:

faldaprevir

,

BI201335

,

Hepatitis C



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.
Advocate1955
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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.