High Rates of SVR Demonstrated in Phase II Study with Investigational Triple DAA Regimen of Daclatasvir, Asunaprevir and BMS

 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

  PR Newswire

  PRINCETON, New Jersey, April 23, 2013

PRINCETON, New Jersey, April 23, 2013 /PRNewswire/ --

  *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

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 [12] ). 

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 SVR [24] and/or
    SVR [36] . 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 SVR [4.] Three out of the 34 patients
    experienced virologic failure on or after treatment. 

                          Group 1    Group 2   Group 3   Group 4

                           (n=16)    (n=16)    (n=16)     (n=18)
    BMS-791325 Dose        75 mg      75 mg    150 mg     150 mg
    Treatment Duration    24 weeks  12 weeks  24 weeks   12 weeks
                           94%[a]    94%[b]      94%    89%[c],[d]

    SVR4                  (15/16)    (15/16)   (15/16)   (16/18)
                           94%[a]    94%[b]             89%[c],[d]

    SVR12                 (15/16)    (15/16)    N/A*     (16/18)
                         88%[a],[b]  94%[b]

    SVR24                 (14/16)    (15/16)     N/A       N/A
                                     88%[e]

    SVR36                   N/A      (14/16)     N/A       N/A
                                                 6%         6%

    Viral Breakthrough       0%        0%      (1/16)     (1/18)
                                                            6%

    Relapse                  0%        0%        0%       (1/18)

^[ ^a ^] Patient withdrew consent;  ^[ ^b ^] One patient missed this visit
but had achieved undetectable viral load at end of treatment or SVR at earlier
endpoints; ^[ ^c ^] One patient experienced viral breakthrough;  ^[ ^d ^] One
patient relapsed;  ^[ ^e ^] Two 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.

Contacts: Media:    Sonia Choi, +1-609-213-6015, sonia.choi@bms.com Carrie
Fernandez, +1-215-859-2605, carrie.fernandez@bms.com Investors: John Elicker,
+1-609-252-4611, john.elicker@bms.com Ranya Dajani, +1-609-252-5330,
ranya.dajani@bms.com Ryan Asay, +1-609-252-5020, ryan.asay@bms.com
 
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