Milvexian demonstrated efficacy and no
increase in bleeding across doses, with no major bleeds in the
milvexian arms, when compared with enoxaparin, for postoperative
venous thromboembolism (VTE) prevention in patients undergoing
elective total knee replacement (TKR) surgery
AXIOMATIC-TKR is the first of two studies to
read out from the Phase 2 milvexian program, which together will
inform the design and dose regimens of the Phase 3 program
Data simultaneously published in The New
England Journal of Medicine and presented at the American Heart
Association Scientific Sessions 2021
Milvexian is being developed by The Bristol
Myers Squibb-Janssen Collaboration
Bristol Myers Squibb (NYSE:BMY) in collaboration with Janssen
Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies
of Johnson and Johnson (Janssen), today announced results from the
Phase 2 AXIOMATIC-TKR study, which showed investigational oral
milvexian reduced the risk of postoperative venous thromboembolism
(VTE) in a dose dependent manner without increasing the risk of
bleeding compared with enoxaparin in patients undergoing total knee
replacement (TKR) surgery. These data were presented today at a
Late-Breaking Science session at the American Heart Association
(AHA) Scientific Sessions 2021 and simultaneously published in The
New England Journal of Medicine (NEJM).
“This study establishes proof-of-principle for milvexian as a
differentiated antithrombotic agent,” said Jeffrey Weitz, M.D.,
Professor of Medicine & Biochemistry and Biomedical Sciences at
McMaster University and Executive Director of the Thrombosis and
Atherosclerosis Research Institute. “Furthermore, the consistently
low rates of bleeding across a 16-fold range of milvexian doses
suggest that it has a wide therapeutic window, which opens the
opportunity to explore milvexian across a broad range of patients,
including those for whom factor Xa inhibitors are underutilized or
not indicated.”
The trial met both of its pre-specified proof-of-principle
requirements: the dose response for efficacy with twice-daily
milvexian was significant (p<0.001), and the 12% rate of VTE
with combined twice-daily doses of milvexian was significantly
lower (p<0.0001) than the prespecified benchmark rate of
30%.
At daily doses of at least 100 mg, the rates of VTE with
milvexian were significantly lower than with enoxaparin
(p≤0.014).
Milvexian
Twice Daily
Milvexian
Once Daily
Enoxaparin Once Daily
25 mg
50 mg
100 mg
200 mg
25 mg
50 mg
200 mg
40 mg
No. of patients evaluated
129
124
134
131
28
127
123
252
Venous thromboembolism*
21%
11%
9%
8%
25%
24%
7%
21%
No. of patients evaluated†
148
148
149
148
33
150
147
296
Any bleeding
1%
5%
5%
3%
0
5%
6%
4%
Major or clinically relevant nonmajor
bleeding
0
1%
1%
1%
0
1%
1%
2%
Major bleeding
0
0
0
0
0
0
0
0.3%
*Primary efficacy outcome defined as the
composite of asymptomatic deep-vein thrombosis (detected by
mandatory unilateral venography performed 10 to 14 days after
surgery) confirmed symptomatic venous thromboembolism (symptomatic
deep-vein thrombosis of the leg or nonfatal pulmonary embolism) or
death.
† Safety outcomes were assessed in the
safety population, which consisted of all patients who received at
least one dose of trial medication.
There were no major bleeds with milvexian and one with
enoxaparin. The rates of major plus clinically relevant non-major
bleeds (CRNM) with milvexian and enoxaparin were 0.8% and 1.4%,
respectively. Across a 16-fold range of doses, milvexian
demonstrated a low risk of major plus CRNM bleeding, with no major
bleeds and no dose-response on this composite outcome.
“We are encouraged by the results of the milvexian TKR trial,
which are consistent with our scientific understanding of the FXIa
mechanism,” said Roland Chen, M.D., senior vice president and head
of cardiovascular development, global drug development at Bristol
Myers Squibb. “The clear dose efficacy response without increased
bleeding provides additional evidence to support our belief in the
promise of milvexian. We look forward to results from our second
Phase 2 trial of milvexian for secondary stroke prevention, which
will add to our body of evidence for milvexian and help inform our
Phase 3 development program.”
The TKR study is the first of two studies to read out from the
Phase 2 milvexian program. Results from the ongoing Phase 2 study
of milvexian for secondary stroke prevention (AXIOMATIC-SSP) are
expected in the first half of 2022. Bristol Myers Squibb and
Janssen thank the patients and investigators involved in this
clinical trial.
About AXIOMATIC-TKR
AXIOMATIC-TKR is a Phase 2, randomized, open-label,
parallel-group, dose-ranging multicenter study that evaluated the
efficacy and safety of milvexian, an oral factor XIa (FXIa)
inhibitor, versus subcutaneous enoxaparin in patients undergoing
elective TKR surgery. The primary efficacy outcome was the
incidence of total VTE up to 14 days. The principal safety outcome
was any bleeding, defined as the composite of major, clinically
relevant nonmajor and minimal bleeding.
A total of 1,242 patients were randomized to receive one of
seven regimens of oral milvexian given twice or once-daily or to
receive 40 mg of subcutaneous enoxaparin once-daily. The assignment
to milvexian or enoxaparin was open label but the milvexian dose
assignment was blinded. Treatment was given for 10-14 days. More
information can be found on www.clinicaltrials.gov
(NCT03891524).
About Milvexian*
Milvexian is a potential first-in-class oral factor XIa (FXIa)
inhibitor (anti-thrombotic) for the prevention and treatment of
major thrombotic conditions. Phase 2 TKR data, complementing human
genetic, epidemiologic and preclinical evidence, now provide
further support for the hypothesis that inhibiting FXIa can reduce
the risk of vascular events without increasing the risk of
bleeding. The milvexian Phase 2 clinical trial program consists of
two Phase 2 studies: AXIOMATIC-TKR (NCT03891524) evaluating
milvexian in TKR surgery and AXIOMATIC-SSP (NCT03766581) evaluating
milvexian for secondary stroke prevention (SSP).
*Milvexian is an investigational agent and has not been approved
for use in any country, for any indication.
About the Bristol Myers Squibb/Janssen Collaboration
Bristol Myers Squibb and Janssen Pharmaceuticals, Inc., two
leaders in thrombosis treatment and care, are collaborating to
develop and commercialize milvexian, a potentially first-in-class
oral factor XIa (FXIa) inhibitor, with the goal of improving upon
the benefit/risk profile of existing anticoagulants. With extensive
expertise and unparalleled leadership in cardiovascular treatments
spanning decades, Bristol Myers Squibb and Janssen share a
long-standing commitment to improving treatment options for
patients with life-threatening cardiovascular conditions.
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 about Bristol Myers Squibb, visit us at BMS.com or
follow us on LinkedIn, Twitter, YouTube, Facebook and
Instagram.
Celgene and Juno Therapeutics are wholly owned subsidiaries of
Bristol-Myers Squibb Company. In certain countries outside the
U.S., due to local laws, Celgene and Juno Therapeutics are referred
to as, Celgene, a Bristol Myers Squibb company and Juno
Therapeutics, a Bristol Myers Squibb company.
Cautionary Statement Regarding Forward-Looking
Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on historical performance and current expectations and
projections about our future financial results, goals, plans and
objectives and involve inherent risks, assumptions and
uncertainties, including internal or external factors that could
delay, divert or change any of them in the next several years, that
are difficult to predict, may be beyond our control and could cause
our future financial results, goals, plans and objectives to differ
materially from those expressed in, or implied by, the statements.
These risks, assumptions, uncertainties and other factors include,
among others, that future study results will be consistent with the
results to date, that milvexian may not achieve its primary study
endpoints or receive regulatory approval for the indication
described in this release in the currently anticipated timeline or
at all, that any marketing approvals, if granted, may have
significant limitations on their use, and, if approved, whether
such product candidate for such indication described in this
release will become commercially successful. No forward-looking
statement can be guaranteed. Forward-looking statements in this
press release should be evaluated together with the many risks and
uncertainties that affect Bristol Myers Squibb’s business and
market, particularly those identified in the cautionary statement
and risk factors discussion in Bristol Myers Squibb’s Annual Report
on Form 10-K for the year ended December 31, 2020, as updated by
our subsequent Quarterly Reports on Form 10-Q, Current Reports on
Form 8-K and other filings with the Securities and Exchange
Commission. The forward-looking statements included in this
document are made only as of the date of this document and except
as otherwise required by applicable law, Bristol Myers Squibb
undertakes no obligation to publicly update or revise any
forward-looking statement, whether as a result of new information,
future events, changed circumstances or otherwise.
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