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 Infe

Princeton, New Jersey (ots/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 [http://www.bms.com ] 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 48th 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 [http://www.bms.com/ourcompany/lead
ership/Pages/brian_daniels_bio.aspx ], MD, senior vice president,
Global Development and Medical Affairs, Research and Development
[http://www.bms.com/research/Pages/home.aspx ], 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 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 withdrewconsent; [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
(greater than or equal to10% 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

ots Originaltext: Bristol-Myers Squibb GmbH & Co.KG aA
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