New Data is Presented on Investigational Oral Anticoagulant Apixaban in Acute Coronary...

New Data is Presented on Investigational Oral Anticoagulant Apixaban in Acute Coronary Syndrome Patients

Dose-Ranging Study Examined Apixaban in Patients Taking Commonly
Used Anti-Platelet Therapies
PRINCETON, N.J. & NEW YORK--(Business Wire)--
Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc (NYSE:
PFE) announced today the results of a Phase 2 dose-ranging study
(APPRAISE-1) involving the investigational compound apixaban in
patients with acute coronary syndrome (ACS, commonly known as heart
attack or severe chest pain). The study compared the current standard
of care for ACS, including aspirin and clopidogrel, with apixaban on
top of the standard of care. The study results were presented during a
late-breaking session at the annual European Society of Cardiology
(ESC) meeting in Munich, Germany.

Apixaban, which is currently being developed by the two companies,
is an investigational oral, highly selective factor Xa inhibitor, a
new class of agents with therapeutic potential to prevent and treat
blood clots in the veins and arteries.

"The APPRAISE-1 study provided encouraging trends suggesting that
anticoagulation with apixaban on top of current standards of care and
continued beyond the initial hospitalization period may reduce the
risk of a second heart attack, stroke or death. As with all effective
anticoagulants, there was a trade off with some increase in bleeding
for reduction in risk. We look forward to further studies of apixaban
in patients with ACS to fully understand its potential beyond current
therapies in this population," said John H. Alexander, M.D., Principal
Investigator of the APPRAISE-1 study, Duke Clinical Research Institute
and Duke Heart Center in Durham, North Carolina.

The six-month APPRAISE-1 study was not powered to demonstrate
significance on the composite efficacy endpoint of cardiovascular
death, non-fatal heart attack, severe recurrent ischemia and
non-hemorrhagic stroke. However, there was a non-significant relative
risk reduction compared to placebo (n=611) of 27 percent for 2.5 mg
twice daily (n=317) and 39 percent for 10 mg once daily (n= 318)
doses.

The incidence of the primary endpoint of this safety study, major
bleeding plus clinically relevant non-major bleeding, was 5.7 percent
for apixaban patients who took the 2.5 mg twice daily dose (n=315),
7.9 percent for patients who took the 10 mg once daily dose (n=315),
and 3.0 percent for patients who took placebo (n=599). The bleeding
scale used in the APPRAISE-1 trial was the comprehensive International
Society of Thrombosis and Haemostasis (ISTH) standard. The incidence
of major ISTH bleeding was 0.8 percent with placebo (n=599) versus 1.6
and 1.9 percent with the 2.5 mg twice daily (n=315) and 10 mg once
daily (n=315) doses, respectively. Results for major bleeding measured
using the more commonly used TIMI scale, in a post-hoc assessment,
were 0.3 percent (n=599) for placebo, 0.0 percent (n=315) for the 2.5
mg twice daily apixaban dose and 1.0 percent (n= 315) for the 10 mg
once daily apixaban dose. Two additional arms of the study that
examined higher doses, 10 mg twice daily and 20 mg once daily, were
stopped early due to increased total bleeding.

The incidence of adverse events, serious adverse events and
discontinuations due to adverse events was similar for all treatment
groups. The discontinuation rates for bleeding events were 1.2 percent
with placebo, 1.9 percent with the 2.5 mg twice daily dose and 2.9
percent with the 10 mg once daily dose. The incidence of liver
function test abnormalities following six-month dosing was similar
with apixaban and placebo. The frequencies of alanine aminotransferase
(ALT) elevations above 3-fold the upper limit of normal were 2.7, 0,
and 1.0 percent for the placebo, 2.5 mg twice daily apixaban, and 10
mg once daily apixaban groups, respectively.

"This important study helps to identify appropriate apixaban
dosing for future studies, with the goal of balancing potential
efficacy benefit while minimizing the risk of bleeding for ACS
patients," said Jack Lawrence, vice president, Research and
Development, Bristol-Myers Squibb. "The objective is to identify
whether apixaban can reduce the risk of secondary cardiovascular
events, offering significant improvements for patient lives, as well
as reducing the economic burden of cardiovascular disease around the
world."

About the APPRAISE-1 Study

The study was a double-blind, placebo-controlled, dose-ranging
study to evaluate the safety and efficacy of apixaban (2.5 mg twice
daily, 10 mg once daily, 10 mg twice daily, or 20 mg once daily) over
a 26-week treatment period in 1715 patients presenting with acute
coronary syndrome (ACS). All patients received aspirin less than or
equal to 165 mg/day. The use of clopidogrel was left to the discretion
of the treating physician. The primary endpoint of the study was the
incidence of ISTH-defined major bleeding and clinically relevant
non-major bleeding. The composite efficacy endpoint was the amount of
time from patient randomization to the first occurrence of a
combination of cardiovascular events including cardiovascular death,
non-fatal heart attack, severe recurrent ischemia and non-hemorrhagic
stroke.

Acute Coronary Syndrome (ACS)

Acute coronary syndrome (ACS) is a life-threatening form of
coronary heart disease (CHD) that occurs when the heart muscle does
not receive enough oxygen-rich blood. ACS includes myocardial
infarction (MI), also known as a heart attack, and unstable angina, or
sudden, severe chest pain that typically occurs when a person is at
rest. Every year, ACS affects an estimated 1.4 million people in the
United States and an estimated 1.40 million people in Europe. Even
though patients are treated with intense management of ACS in the
hospital setting, there still remains an unmet need for new treatments
that can reduce the significant residual risk of acute MI, stroke and
cardiovascular death. Patients with an ACS event are often given IV or
injectable anticoagulants but, due to the route of administration, the
use of these agents is limited to the hospital.

About the Apixaban Clinical Trial Program

Apixaban is currently being explored in the EXPANSE clinical trial
program which includes eight Phase III clinical studies involving
approximately 45,000 patients worldwide. The ADVANCE-2 and 3 trials
are investigating the safety and efficacy of apixaban 2.5 mg twice
daily compared to enoxaparin 40 mg once daily in patients undergoing
major orthopedic surgery. The ADOPT study is investigating apixaban
for one month compared to standard of care (enoxaparin 40 mg once
daily for at least 6 days followed by placebo) for the prevention of
VTE in hospitalized patients who are medically ill and at risk of VTE.

Apixaban is also in Phase III trials studying the prevention of
stroke and other thromboembolic events in patients with atrial
fibrillation (AF) and studying the treatment of VTE. The AF program
consists of two trials. The ARISTOTLE trial is investigating apixaban
compared to warfarin in approximately 15,000 patients with atrial
fibrillation. The AVERROES trial is investigating apixaban compared to
aspirin in approximately 5,600 patients with atrial fibrillation who
are ineligible for vitamin K antagonists (VKA) treatment or haven't
tolerated previous VKA treatment.

The VTE treatment program consists of two trials. The AMPLIFY
trial is a 6-month trial investigating apixaban compared to enoxaparin
plus warfarin in approximately 4,800 patients with acute DVT or PE.
The AMPLIFY-EXT trial is a 12-month trial investigating apixaban
compared to placebo for extended treatment to prevent recurrent VTE in
approximately 2,400 patients who have completed 6 to 12 months of
treatment for DVT or PE.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to extend and enhance human life. For more information
visit www.bms.com.

About Pfizer

Founded in 1849, Pfizer is the world's largest research-based
pharmaceutical company. Pfizer is taking new approaches to advancing
better health as it discovers, develops, manufactures and delivers
quality, safe and effective prescription medicines to treat and help
prevent disease for both people and animals. For more information
visit www.pfizer.com.

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
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
described in this release will support a regulatory filing or that the
product will receive regulatory approval. There can be no assurance
that if approved, the products described in this release will be
commercially successful. Forward-looking statements in the 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, 2007, its
Quarterly Reports on Form 10-Q, and 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.

Pfizer Forward-Looking Statement

The information contained in this release is as of August 26,
2008. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new information
or future events or developments.

This release contains forward-looking information about a product
candidate, apixaban, including its potential benefits that involves
substantial risks and uncertainties. Such risks and uncertainties
include, among other things, the uncertainties inherent in research
and development; decisions by regulatory authorities regarding whether
and when to approve any drug applications that may be filed for such
product candidate as well as their decisions regarding labeling and
other matters that could affect its availability or commercial
potential; and competitive developments.

A further description of risks and uncertainties can be found in
Pfizer's Annual Report on Form 10-K for the fiscal year ended December
31, 2007 and in its reports on Form 10-Q and Form 8-K.

Media:
BMS
Laura Hortas, 609-252-4587
laura.hortas@bms.com
or
Pfizer
Vanessa Aristide, 212-733-3784
vanessa.aristide@pfizer.com
or
Pfizer/onsite
Oliver Stohlmann, +43-1-52115-337
Oliver.stohlmann@pfizer.com
or
Investors:
BMS
John Elicker, 212-546-3775
john.elicker@bms.com
or
Pfizer
Jennifer Davis, 212-733-0717
jennifer.m.davis@pfizer.com

Copyright Business Wire 2008