High Rates of SVR Demonstrated in Phase II Study with Investigational Triple DAA Regimen of Daclatasvir, Asunaprevir and BMS-791325 in Treatment-Naïve Patients with Genotype 1 Chronic Hepatitis C Infection

• This all-oral treatment regimen is being studied as an interferon-free and ribavirin-free option
• Investigational regimen involves three different classes of direct-acting antivirals (DAAs) - an NS5A replication complex inhibitor, an NS3 protease inhibitor and an NS5B non-nucleoside polymerase inhibitor
• Phase III development as a fixed-dose combination is anticipated to begin by late 2013

PRINCETON, NJ, April 23, 2013 /CNW/ - Bristol-Myers Squibb Company (NYSE: BMY) today announced additional, interim Phase II data demonstrating that 12- and 24-week Triple DAA treatment regimens of daclatasvir (DCV), asunaprevir (ASV) and BMS-791325 ('325) achieved high rates of sustained virologic response (SVR) of up to 94%, in treatment-naïve, genotype 1 chronic hepatitis C patients, at time points ranging from 4 to 36 weeks post-treatment depending on the treatment group.  These data support the continued development of this interferon alfa-, ribavirin (RBV)- and ritonavir (RTV)-free regimen, with Phase III initiation anticipated to begin by late 2013.

The study results will be presented this week at the International Liver Congress, the 48^th annual meeting of the European Association for the Study of the Liver (EASL), in Amsterdam.

Two serious adverse events (2/66), renal calculus and cerebral vasoconstriction, were reported in this study.  The renal calculus was determined by the investigator to be unrelated to study drug.  The cerebral vasoconstriction was associated with treatment intensification with peginterferon alfa and ribavirin following viral breakthrough in one patient.  Headache was the most common adverse event in the study (27.3%, 18/66).

"The diversity of the hepatitis C patient population requires multiple treatment options that can enable a personalized approach to therapy.  Effective and well-tolerated oral treatment regimens that are ribavirin-free remain an important unmet medical need in hepatitis C," said Brian Daniels, MD, senior vice president, Global Development and Medical Affairs, Research and Development, Bristol-Myers Squibb.  "These data, which demonstrate comparable efficacy among the 12- and 24-week Triple DAA treatment groups, support the rapid Phase III development of this investigational Triple DAA regimen and provide further data on daclatasvir as an important component of DAA-based therapy."

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. BMS-791325 is a non-nucleoside inhibitor of the NS5B polymerase, currently in Phase II development for hepatitis C as a component of daclatasvir-based treatment regimens.

Study Design and Results

This open-label, two-part Phase II study is designed to evaluate the safety and antiviral activity of the investigational hepatitis C treatment regimen of DCV, ASV and '325 in treatment-naïve patients with genotype 1a and 1b chronic hepatitis C infection.  The primary endpoint of the study is viral load below the lower limit of quantitation (LLOQ; HCV RNA 25 IU/mL) at 12 weeks post-treatment (SVR₁₂).

Part 1 of the study evaluated a treatment regimen of DCV 60 mg QD, ASV 200 mg BID and '325 75 mg BID for 24 or 12 weeks (Groups 1 and 2, respectively).  Part 2 of the study evaluated the same DAA regimen for 24 or 12 weeks, with '325 dosed at 150 mg BID (Groups 3 and 4, respectively).

Interim results for Part 1 of the study were previously reported at the American Association for the Study of the Liver (AASLD) annual meeting in November 2012.

The study was expanded in November 2012, adding eight new treatment groups including the evaluation of this Triple DAA regimen in treatment-naïve patients with HCV genotype 4 and null responders with HCV genotype 1.  Results from these treatment groups are not yet available.

Virologic Response

• 100% (28/28) of patients in Groups 1 and 2 (24- and 12-week treatment, '325 75 mg) with post-treatment follow-up data achieved SVR₂₄ and/or SVR₃₆.  There was no viral breakthrough during treatment and no post-treatment relapse in either group.
  
  
• 91% (31/34) of patients overall in Groups 3 and 4 (24- and 12-week treatment, '325 150 mg) achieved SVR₄; Three out of the 34 patients experienced virologic failure on or after treatment.
  
  
  

	Group 1 (n=16)	Group 2 (n=16)	Group 3 (n=16)	Group 4 (n=18)
BMS-791325 Dose	75 mg	75 mg	150 mg	150 mg
Treatment Duration	24 weeks	12 weeks	24 weeks	12 weeks
SVR4	94%^a (15/16)	94%^b (15/16)	94% (15/16)	89%^c,d (16/18)
SVR12	94%^a (15/16)	94%^b (15/16)	N/A*	89%^c,d (16/18)
SVR24	88%^a,b (14/16)	94%^b (15/16)	N/A	N/A
SVR36	N/A	88%^e (14/16)	N/A	N/A
Viral Breakthrough	0%	0%	6% (1/16)	6% (1/18)
Relapse	0%	0%	0%	6% (1/18)

^aPatient withdrew consent; ^bOne patient missed this visit but had achieved undetectable viral load at end of treatment or SVR at earlier endpoints; ^cOne patient experienced viral breakthrough; ^dOne patient relapsed; ^eTwo patients missed this visit, but had achieved SVR at earlier endpoints
* N/A = data not available at time of analysis

On-Treatment Safety

There were no deaths and no patient discontinuations due to treatment intolerance or adverse events (AEs) related to BMS therapy.  Two serious adverse events (SAEs) were reported in the study.  One SAE, cerebral vasoconstriction, occurred in Group 3 during treatment intensification with peginterferon alfa and RBV following viral breakthrough and lead to treatment discontinuation; cerebral vasoconstriction is a known side effect of interferon alfa.  The remaining SAE reported on-treatment, renal calculus, was observed in Group 2 and was determined by the investigator to be unrelated to study drug.

Most AEs were mild to moderate in severity.  The most common AEs (≥10% total) across all study groups were headache (27.3%, 18/66), asthenia (16.7%, 11/66), diarrhea (16.7%, 11/66), and nausea (13.6%, 9/66).

No Grade 3-4 elevations in liver enzymes (ALT/AST) or bilirubin were observed in this study.  One grade 3 AE (headache) resolved after seven days with continued study treatment.  One grade 3-4 laboratory abnormality was reported in this study.  One case of lymphopenia was recorded in Group 2 at a single study visit concomitant with influenza.  All other AEs were grade 1 or 2.

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 direct-acting antivirals. 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 4,100 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 2,000 patients to date.  BMS-791325 is a non-nucleoside inhibitor of the NS5B polymerase, currently in Phase II development for hepatitis C as a component of daclatasvir-based treatment regimens that has been studied in more than 300 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 clinical trials of these compounds will support regulatory filings, or that the compounds will receive regulatory approvals or, if approved, that 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, 2012, 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. 

 

SOURCE: Bristol-Myers Squibb

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