Investigational Triple DAA Regimen of Daclatasvir, Asunaprevir and BMS-791325 Achieved SVR12 of 94% in Treatment-Naïve Patients

  Investigational Triple DAA Regimen of Daclatasvir, Asunaprevir and
  BMS-791325 Achieved SVR12 of 94% in Treatment-Naïve Patients with Genotype 1
  Chronic Hepatitis C Infection in Phase II Trial

  *First presentation of results from this investigational interferon-,
    ribavirin- and ritonavir-free regimen
  *Phase III development anticipated to begin in 2014
  *Triple DAA regimen is one of multiple daclatasvir-based regimens in
    development to help address unmet needs of diverse HCV patient population

Business Wire

BOSTON -- November 12, 2012

Bristol-Myers Squibb Company (NYSE: BMY) today announced for the first time
Phase II data demonstrating that the 12-week Triple DAA treatment regimen of
daclatasvir (DCV), asunaprevir (ASV), and BMS-791325 achieved sustained
virologic response 12 weeks post-treatment (SVR[12]) in 94% (15/16) of
treatment-naïve, genotype 1 chronic hepatitis C patients. The remaining one
patient had undetectable viral load at the end of treatment and was lost to
follow-up until approximately 24 weeks post-treatment; in preliminary data,
this patient has achieved SVR[24]. The Phase II results from this interferon-,
ribavirin- and ritonavir-free investigational regimen combining three
different classes of direct-acting antivirals (DAAs) – an NS5A replication
complex inhibitor (DCV), an NS3 protease inhibitor (ASV) and an NS5B
non-nucleoside polymerase inhibitor (BMS-791325) – were presented today at the
American Association for the Study of Liver Diseases congress in Boston.

One serious adverse event was reported in this study and was determined by the
investigator to be unrelated to study drug. There were no discontinuations due
to adverse events. Headache was the most common adverse event in the study
(31%, 10/32).

“We are encouraged that this 12-week daclatasvir-based regimen with compounds
in different classes of DAAs achieved SVR[12] in a majority of patients
without the use of interferon, ribavirin or ritonavir,” said Brian Daniels,
MD, senior vice president, Global Development and Medical Affairs, Research
and Development, Bristol-Myers Squibb. “The development of regimens for
hepatitis C with the potential to avoid the use of ribavirin and ritonavir is
an important approach in this therapeutic area, and we look forward to
studying it further.”

Phase II studies of this investigational Triple DAA regimen are ongoing. Phase
III development is anticipated to begin in 2014.

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 BMS-791325 in treatment-naïve patients with genotype 1 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 (SVR[12]).

Data presented at AASLD are from an interim analysis of Part 1 of the study.
In Part 1, 32 patients were randomized 1:1 (n=16/arm) into two groups.

  *Group 1: 24 weeks of treatment with DCV 60 mg QD, ASV 200 mg BID,
    BMS-791325 75 mg BID
  *Group 2: 12 weeks of treatment with DCV 60 mg QD, ASV 200 mg BID,
    BMS-791325 75 mg BID

In Part 2 of the study, patients were assigned to the same DAA regimen for 24
or 12 weeks, with BMS-791325 dosed at 150 mg BID (Groups 3 and 4,
respectively). Part 2 is ongoing and results are not yet available.

Virologic Response

  *Group 1 (24 week treatment): 94% (15/16) achieved undetectable viral load
    by the end of treatment and sustained through SVR[4]. Two patients
    discontinued study drugs prior to the protocol-defined last treatment
    visit, one due to inability to comply with study procedures (poor venous
    access) who achieved SVR[4], and one withdrew consent and is lost to
    follow up.
  *Group 2 (12 week treatment): 100% (16/16) achieved undetectable viral load
    by the end of treatment and 94% (15/16) achieved SVR[12]. The remaining
    one patient was lost to follow-up after completing treatment but did
    return approximately 24 weeks post treatment and in preliminary data, has
    achieved SVR[24]. One patient discontinued study drugs prior to the
    protocol-defined last treatment visit (due to poor/non-compliance) and
    achieved SVR[12].
  *Viral load declined rapidly in both groups and was below LLOQ in all
    patients (32/32) by week 4.
  *There was no viral breakthrough during treatment and no post-treatment
    relapse.

Safety

There were no deaths, discontinuations due to adverse events (AEs), or serious
adverse events (SAEs) due to study drugs. Most AEs were mild to moderate in
severity. The most common AEs (≥10% total) were headache (Group 1: 25%, 4/16;
Group 2: 38%, 6/16), diarrhea (Group 1: 13%, 2/16; Group 2: 38%, 6/16), and
asthenia (Group 1: 13%, 2/16; Group 2: 19%, 3/16).

No Grade 3-4 elevations in liver enzymes (ALT/AST) or bilirubin were observed.
One grade 3 AE (headache) resolved after seven days with continued study
treatment and one grade 3–4 laboratory abnormality (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 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. 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.

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 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.

Contact:

Bristol-Myers Squibb
Media:
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
Sonia Choi, 609-252-5132
sonia.choi@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com
Ranya Dajani, 609-252-5330
ranya.dajani@bms.com
Ryan Asay, 609-252-5020
ryan.asay@bms.com
 
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