-- Apixaban Phase II Acute Coronary Syndrome Data to be Presented at European Society of Cardiology Meeting on Sept. 2
-- U.S. Regulatory Filing for the Prevention of Venous Thromboembolism will not be submitted in 2009, as previously indicated
-- Other Clinical Programs Continue as Planned
Bristol-Myers Squibb Company (NYSE: BMY) and Pfizer Inc (NYSE: PFE)
provided an update on the apixaban clinical development program today.
The companies announced that new Phase II data in acute coronary
syndrome patients (ACS) will be presented at the upcoming meeting of the
European Society of Cardiology (ESC). In addition, Bristol-Myers Squibb
and Pfizer reported that an early evaluation of results from a Phase III
study of apixaban for the prevention of venous thromboembolism (VTE) in
patients undergoing total knee replacement indicates that the primary
endpoint of this study was not met.
The Phase III VTE prevention study known as ADVANCE-1 compared apixaban,
a novel, oral Factor Xa inhibitor given at a dose of 2.5 mg, twice
daily, to the FDA-approved dose of enoxaparin, 30 mg given twice daily.
The primary efficacy outcome was a composite of symptomatic or
asymptomatic deep vein thrombosis, pulmonary embolism, and death by any
cause. The rate of the primary efficacy endpoint on apixaban was
numerically similar to that observed with enoxaparin (9.0% vs. 8.9%,
p=.064), but did not meet the pre-specified statistical criteria for
non-inferiority compared to enoxaparin. The actual enoxaparin VTE rate
of 8.9 percent was lower than the expected VTE rate of 16 percent seen
in previous similar clinical trials, resulting in an inability to
demonstrate non-inferiority.
In ADVANCE-1, there were no unexpected findings in adverse events for
apixaban compared to enoxaparin. The major bleeding event rate for
apixaban was numerically lower, but was not significantly lower, than
enoxaparin (0.7% vs. 1.4%, p=.053). The composite rate of clinically
relevant non-major bleeding and major bleeding was significantly less in
patients who received apixaban than those who received enoxaparin (2.9%
vs. 4.3%, p =.034).
Full results of the ADVANCE-1 trial have been submitted to the American
Society of Hematology Meeting (ASH) for presentation in December.
ADVANCE-1 results confirm the characteristics of apixaban as reported
previously in phase II studies. The companies are considering further
studies with different protocols in preventing VTE in knee surgery and
will not submit the U.S. filing for VTE prevention in the 2nd
half of 2009, as previously communicated. The results of ADVANCE -1 do
not necessitate any changes in protocols of any other ongoing apixaban
studies. Programs directed towards prevention of VTE including EMEA
registrational studies, treatment of VTE, and in the prevention of
stroke in atrial fibrillation continue as planned.
“Bristol-Myers Squibb and Pfizer remain
enthusiastic and committed to the clinical development program for
apixaban,” said Jack Lawrence, vice president,
Research and Development, Bristol-Myers Squibb. “Bristol-Myers
Squibb and Pfizer anticipate that the results of APPRAISE-1 being
presented at ESC will provide important insight into the potential use
of apixaban for the secondary prevention of cardiovascular events in
patients with acute coronary syndrome, which affects an estimated 2.7
million people around the world every year.”About the Apixaban Clinical Program
Apixaban, an oral, factor Xa inhibitor in a new class of agents that
have shown therapeutic potential to prevent and treat blood clots, 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). 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
product 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.