April 19, 2012 12:00 PM Eastern Daylight Time
All-Oral Hepatitis C Virus Treatment with Bristol-Myers Squibb’s Investigational Compounds Daclatasvir and Asunaprevir Achieved Sustained Virologic Response in 77% of Difficult-to-Treat Patients
All-Oral Hepatitis C Virus Treatment with Bristol-Myers Squibb’s Investigational Compounds Daclatasvir and Asunaprevir Achieved Sustained Virologic Response in 77% of Difficult-to-Treat Patients
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- Dual oral therapy data demonstrates SVR24 in genotype 1b difficult-to-treat patients, including null responders and patients medically ineligible or intolerant to alfa and ribavirin
- Study confirms the sentinel cohort data reported at AASLD in 2011
- Data presented at The International Liver Congress in Barcelona
PRINCETON, N.J.--()--Bristol-Myers Squibb Company (NYSE: BMY) today announced results from a Phase II study in which treatment with an all-oral, dual direct-acting antiviral (DAA) regimen of daclatasvir, an investigational NS5A replication complex inhibitor, and asunaprevir, an investigational NS3 protease inhibitor, achieved undetectable viral load 24 weeks post-treatment (SVR24) in 77% (33/43) of difficult-to-treat genotype 1b hepatitis C (HCV) patients. Difficult-to-treat patients in this study included null responders, or patients who had previously not responded to treatment with peginterferon alfa and ribavirin (alfa/RBV), and patients who were medically ineligible or intolerant to previous treatment with alfa/RBV. In this study, serious adverse events (SAE) included three patients with fever (pyrexia), one with hypochondriasis, and one with hyperbilirubinemia which led to treatment discontinuation. The study findings, presented in an oral session at the International Liver Congress (ILC), the 47th annual meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain, confirmed the previously announced sentinel cohort data.
“Currently there are no treatments available for hepatitis C genotype 1 that can be administered without the concurrent use of alfa and ribavirin, which gives rise to a serious unmet need for patients who are ineligible or intolerant to alfa/ribavirin,” said principal investigator Fumitaka Suzuki, Toranomon Hospital, Tokyo, Japan. “The results of this Phase II study with Bristol-Myers Squibb’s daclatasvir and asunaprevir are encouraging as we study potential hepatitis C therapies for this difficult-to-treat patient population.”
Study Results
The primary endpoint of the study was the proportion of patients with sustained virologic response 12-weeks following treatment (SVR12). In this study, the patents were divided into two treatment groups: Group A consisted of 21 genotype 1b prior null responders and Group B consisted of 22 genotype 1b patients medically ineligible for alfa/RBV or with prior intolerance to alfa/RBV. Overall, 77% (33/43) of patients achieved SVR12 and maintained virologic response through follow-up to SVR24. SVR24 was achieved by 91% (19/21) of patients in Group A and 64% (14/22) of patients in Group B. Of the 43 patients enrolled in the study, 39 completed 24 weeks of treatment. In this study, 94% (33/35) patients who achieved SVR4 remained undetectable SVR24, and 100% (33/33) of patients who achieved SVR12 remained undetectable at SVR24.
Viral breakthrough was observed in 7.0% (3/43) of patients and post-treatment relapse was observed in 9.3% (4/43) of patients in the study. All occurrences of viral breakthrough and post-treatment relapse took place in the alfa/RBV ineligible/intolerant arm. There were no viral breakthroughs and no post-treatment relapses in prior null responders.
Serious adverse events occurred in five patients. Three patients experienced Grade 2/3 fever (pyrexia), one patient developed Grade 2 hypochondriasis, and one patient developed Grade 4 elevated bilirubin levels (hyperbilirubinemia) that led to study discontinuation at week 2. There were three additional discontinuations due to adverse events: two transaminase elevations at weeks 12 and 16 and one lymphopenia at week 52 (off-study) in a patient with alfa/RBV added at week six. The most commonly reported on-treatment adverse events occurring in at least three patients were headache (14/43), nasopharyngitis (14/43), liver enzyme increases (12/43 ALT increase and 10/43 AST increase), diarrhea (Grade 1, 11/43), and fever (pyrexia, 8/43). There were no deaths in this study and no clinically relevant changes in electrocardiogram parameters.
About the Study
In this Phase II open-label clinical trial (AI447-017), an expanded cohort of 43 Japanese patients with chronic HCV genotype 1b infection with null response to prior alfa/RBV treatment (reduction in HCV RNA <2 log10 IU/mL with 12 weeks of alfa/RBV therapy) or patients ineligible for or intolerant to treatment with alfa/RBV were treated with daclatasvir 60 mg once daily and asunaprevir 200 mg twice daily, for 24 weeks. (Asunaprevir was initially dosed 600 mg twice daily in sentinel cohort of 10 null responders.) The primary efficacy endpoint was the proportion of patients with undetectable viral load (HCV RNA < 15 IU/mL) at 12 weeks post-treatment (SVR12). Patients were followed to 24 weeks post-treatment (SVR24).
About Bristol-Myers Squibb’s Commitment to Liver Disease
Bristol-Myers Squibb is studying a portfolio of compounds that aim 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 a portfolio of compounds with different mechanisms of action, pursuing both biologics as well as small molecule antivirals. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies. Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir, also known as BMS-790052, is the first NS5A replication complex inhibitor to be investigated in hepatitis C clinical trials and is currently in Phase III development. Asunaprevir, also known as BMS-650032, is an NS3 protease inhibitor in Phase III development for hepatitis C.
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. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.
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 move from exploratory development into full product development, 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, 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.
Viral breakthrough was observed in 7.0% (3/43) of patients and post-treatment relapse was observed in 9.3% (4/43) of patients in the study. All occurrences of viral breakthrough and post-treatment relapse took place in the alfa/RBV ineligible/intolerant arm. There were no viral breakthroughs and no post-treatment relapses in prior null responders.
Serious adverse events occurred in five patients. Three patients experienced Grade 2/3 fever (pyrexia), one patient developed Grade 2 hypochondriasis, and one patient developed Grade 4 elevated bilirubin levels (hyperbilirubinemia) that led to study discontinuation at week 2. There were three additional discontinuations due to adverse events: two transaminase elevations at weeks 12 and 16 and one lymphopenia at week 52 (off-study) in a patient with alfa/RBV added at week six. The most commonly reported on-treatment adverse events occurring in at least three patients were headache (14/43), nasopharyngitis (14/43), liver enzyme increases (12/43 ALT increase and 10/43 AST increase), diarrhea (Grade 1, 11/43), and fever (pyrexia, 8/43). There were no deaths in this study and no clinically relevant changes in electrocardiogram parameters.
About the Study
In this Phase II open-label clinical trial (AI447-017), an expanded cohort of 43 Japanese patients with chronic HCV genotype 1b infection with null response to prior alfa/RBV treatment (reduction in HCV RNA <2 log10 IU/mL with 12 weeks of alfa/RBV therapy) or patients ineligible for or intolerant to treatment with alfa/RBV were treated with daclatasvir 60 mg once daily and asunaprevir 200 mg twice daily, for 24 weeks. (Asunaprevir was initially dosed 600 mg twice daily in sentinel cohort of 10 null responders.) The primary efficacy endpoint was the proportion of patients with undetectable viral load (HCV RNA < 15 IU/mL) at 12 weeks post-treatment (SVR12). Patients were followed to 24 weeks post-treatment (SVR24).
About Bristol-Myers Squibb’s Commitment to Liver Disease
Bristol-Myers Squibb is studying a portfolio of compounds that aim 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 a portfolio of compounds with different mechanisms of action, pursuing both biologics as well as small molecule antivirals. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies. Discovered by Bristol-Myers Squibb through a genomics approach, daclatasvir, also known as BMS-790052, is the first NS5A replication complex inhibitor to be investigated in hepatitis C clinical trials and is currently in Phase III development. Asunaprevir, also known as BMS-650032, is an NS3 protease inhibitor in Phase III development for hepatitis C.
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. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.
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 move from exploratory development into full product development, 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, 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.
Contacts
Bristol-Myers Squibb
Media:
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
Media:
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
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