Study met primary endpoints of clinical
remission in induction at Week 10 and in maintenance at Week
52
Zeposia is the first oral
sphingosine-1-phosphate (S1P) receptor modulator to demonstrate
benefit in moderate to severe ulcerative colitis in a Phase 3
study
Bristol Myers Squibb (NYSE:BMY) today announced results from
True North, a pivotal Phase 3 trial evaluating oral Zeposia
(ozanimod) as an induction and maintenance therapy for adult
patients with moderate to severe ulcerative colitis. True North met
both primary endpoints, demonstrating highly statistically
significant (p-value < 0.0001) results for induction of clinical
remission at Week 10 and in maintenance at Week 52. The study also
met key secondary endpoints of clinical response and endoscopic
improvement in induction at Week 10 and in maintenance at Week
52.
The safety profile of Zeposia in the True North trial was
consistent with that observed in previously reported trials. The
company will complete a full evaluation of the True North data and
work with investigators to present detailed results at a future
medical meeting, as well as discuss these results with health
authorities.
“Patients with ulcerative colitis can struggle to effectively
manage this often unpredictable and potentially debilitating
disease. The True North results are encouraging for patients living
with moderate to severe ulcerative colitis as Zeposia demonstrated
consistency across key clinical and endoscopic endpoints,
suggesting Zeposia may address the need for new oral therapy
options with a favorable benefit to risk profile in the treatment
journey,” said Samit Hirawat, M.D., chief medical officer, Bristol
Myers Squibb. “At Bristol Myers Squibb, we are committed to
researching innovative treatment options that may elevate the
standard of care for people living with ulcerative colitis, with a
focus on finding solutions that have the potential to transform
outcomes for the inflammatory bowel disease community.”
Bristol Myers Squibb is also investigating Zeposia for the
treatment of moderately to severely active Crohn’s disease in the
ongoing Phase 3 YELLOWSTONE clinical trial program.
About True North
True North is a Phase 3, multicenter, randomized, double-blind,
placebo-controlled trial comparing the efficacy and safety of
Zeposia 1mg in patients with moderate to severe ulcerative colitis
who did not adequately respond to prior treatment. In the induction
phase, cohort 1 patients were randomized 2:1 to Zeposia or placebo
and treated once daily for 10 weeks. Cohort 2 was an open-label
arm, and included to allow adequate patient numbers for the
maintenance phase of the trial. Cohort 2 patients were treated once
daily with Zeposia for 10 weeks.
For the maintenance phase, patients on Zeposia from either
cohort 1 or 2 who achieved clinical response in the induction phase
at Week 10 were re-randomized 1:1 to Zeposia or placebo through
Week 52. Patients on placebo who achieved clinical response in the
induction phase at Week 10 remained on placebo during this blinded
maintenance phase.
All eligible patients were rolled into an open-label extension
trial, which is ongoing and designed to assess the longer-term
profile of Zeposia for the treatment of moderate to severe
ulcerative colitis.
The primary endpoints are the proportion of patients in clinical
remission based on a composite clinical and endoscopic score
(3-component Mayo Score) at Week 10 in the induction phase, and at
Week 52 for the maintenance phase. Secondary endpoints include the
proportion of patients achieving clinical response at Week 10 and
Week 52, the proportion of patients with endoscopic improvement
(endoscopy score ≤1) at Week 10 and Week 52, and clinical remission
at Week 52 in patients that were in remission at Week 10. More
information can be found on www.clinicaltrials.gov,
NCT02435992.
About Ulcerative Colitis
Ulcerative colitis, a chronic inflammatory bowel disease (IBD),
is characterized by an abnormal, prolonged immune response that
creates long-lasting inflammation and ulcers (sores) in the mucosa
(lining) of the large intestine (colon). Symptoms, including bloody
stools, severe diarrhea and frequent abdominal pain, usually
develop over time rather than suddenly. Ulcerative colitis has a
major impact on patients' health-related quality of life, including
physical functioning, social and emotional well-being and ability
to work. Many patients have an inadequate response or do not
respond at all to currently available therapies. It is estimated
that 12.6 million people worldwide have IBD.
About Zeposia (ozanimod)
Zeposia (ozanimod) is an oral, sphingosine 1-phosphate (S1P)
receptor modulator that binds with high affinity to S1P receptors 1
and 5. Zeposia reduces the capacity of lymphocytes to egress from
lymph nodes, reducing the number of circulating lymphocytes in
peripheral blood. The mechanism by which Zeposia exerts therapeutic
effects in ulcerative colitis is unknown but may involve the
reduction of lymphocyte migration into the inflamed intestinal
mucosa.
The U.S. Food and Drug Administration (FDA) approved Zeposia for
the treatment of adults with relapsing forms of multiple sclerosis
(RMS) in March 2020. The European Commission approved Zeposia for
the treatment of adult patients with relapsing remitting multiple
sclerosis (RRMS) with active disease as defined by clinical or
imaging features in May 2020. Zeposia is also in development for
additional immune-inflammatory indications, including Crohn's
disease.
U.S. FDA-APPROVED INDICATION FOR ZEPOSIA
ZEPOSIA is indicated for the treatment of relapsing forms of
multiple sclerosis (MS), to include clinically isolated syndrome,
relapsing-remitting disease, and active secondary progressive
disease, in adults.
IMPORTANT SAFETY INFORMATION
Contraindications:
- Patients who in the last 6 months, experienced myocardial
infarction, unstable angina, stroke, transient ischemic attack
(TIA), decompensated heart failure requiring hospitalization, or
Class III/IV heart failure or have a presence of Mobitz type II
second or third-degree atrioventricular (AV) block, sick sinus
syndrome, or sino-atrial, unless the patient has a functioning
pacemaker
- Patients with severe untreated sleep apnea
- Patients taking a monoamine oxidase (MAO) inhibitor
Infections: ZEPOSIA may increase the susceptibility to
infections. Life-threatening and rare fatal infections have
occurred in patients receiving ZEPOSIA. Obtain a recent (i.e.,
within 6 months or after discontinuation of prior MS therapy)
complete blood count (CBC) including lymphocyte count before
initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with
an active infection until the infection is resolved. Consider
interruption of treatment with ZEPOSIA if a patient develops a
serious infection. Continue monitoring for infections up to 3
months after discontinuing ZEPOSIA
- Herpes zoster was reported as an adverse reaction in ZEPOSIA
-treated patients. Herpes simplex encephalitis and varicella zoster
meningitis have been reported with sphingosine 1-phosphate (S1P)
receptor modulators. Patients without a healthcare
professional-confirmed history of varicella (chickenpox), or
without documentation of a full course of vaccination against
varicella zoster virus (VZV), should be tested for antibodies to
VZV before initiating ZEPOSIA. A full course of vaccination for
antibody-negative patients with varicella vaccine is recommended
prior to commencing treatment with ZEPOSIA
- Cases of fatal cryptococcal meningitis (CM) were reported in
patients treated with another S1P receptor modulator. If CM is
suspected, ZEPOSIA should be suspended until cryptococcal infection
has been excluded. If CM is diagnosed, appropriate treatment should
be initiated.
- Progressive Multifocal Leukoencephalopathy (PML) is an
opportunistic viral infection of the brain that typically occurs in
patients who are immunocompromised, and that usually leads to death
or severe disability. No cases of PML were identified in
active-controlled MS clinical trials with ZEPOSIA. PML has been
reported in patients treated with S1P receptor modulators and other
MS therapies and has been associated with some risk factors. If PML
is suspected, withhold ZEPOSIA and perform an appropriate
diagnostic evaluation. If confirmed, treatment with ZEPOSIA should
be discontinued
- In clinical studies, patients who received ZEPOSIA were not to
receive concomitant treatment with antineoplastic,
non-corticosteroid immunosuppressive, or immune-modulating
therapies used for treatment of MS. Concomitant use of ZEPOSIA with
any of these therapies would be expected to increase the risk of
immunosuppression. When switching to ZEPOSIA from immunosuppressive
medications, consider the duration of their effects and their mode
of action to avoid unintended additive immunosuppressive
effects
- Use of live attenuated vaccines should be avoided during and
for 3 months after treatment with ZEPOSIA. If live attenuated
vaccine immunizations are required, administer at least 1 month
prior to initiation of ZEPOSIA
Bradyarrhythmia and Atrioventricular Conduction Delays:
Since initiation of ZEPOSIA may result in a transient decrease in
heart rate and atrioventricular conduction delays, dose titration
is recommended to help reduce cardiac effects. Initiation of
ZEPOSIA without dose escalation may result in greater decreases in
heart rate. If treatment with ZEPOSIA is considered, advice from a
cardiologist should be sought for those individuals:
- with significant QT prolongation
- with arrhythmias requiring treatment with Class 1a or III
anti-arrhythmic drugs
- with ischemic heart disease, heart failure, history of cardiac
arrest or myocardial infarction, cerebrovascular disease, and
uncontrolled hypertension
- with a history of Mobitz type II second-degree or higher AV
block, sick-sinus syndrome, or sinoatrial heart block
Liver Injury: Elevations of aminotransferases may occur
in patients receiving ZEPOSIA. Obtain liver function tests, if not
recently available (i.e., within 6 months), before initiation of
ZEPOSIA. Patients who develop symptoms suggestive of hepatic
dysfunction should have hepatic enzymes checked and ZEPOSIA should
be discontinued if significant liver injury is confirmed. Caution
should be exercised when using ZEPOSIA in patients with history of
significant liver disease
Fetal Risk: There are no adequate and well-controlled
studies in pregnant women. Based on animal studies, ZEPOSIA may
cause fetal harm. Women of childbearing potential should use
effective contraception to avoid pregnancy during treatment and for
3 months after stopping ZEPOSIA
Increased Blood Pressure: Increase in systolic pressure
was observed after about 3 months of treatment and persisted
throughout treatment. Blood pressure should be monitored during
treatment and managed appropriately. Certain foods that may contain
very high amounts of tyramine could cause severe hypertension in
patients taking ZEPOSIA. Patients should be advised to avoid foods
containing a very large amount of tyramine while taking ZEPOSIA
Respiratory Effects: ZEPOSIA may cause a decline in
pulmonary function. Spirometric evaluation of respiratory function
should be performed during therapy, if clinically indicated
Macular edema: S1P modulators have been associated with
an increased risk of macular edema. Patients with a history of
uveitis or diabetes mellitus are at increased risk. Patients with a
history of these conditions should have an ophthalmic evaluation of
the fundus, including the macula, prior to treatment initiation and
regular follow-up examinations. An ophthalmic evaluation is
recommended in all patients at any time if there is a change in
vision. Continued use of ZEPOSIA in patients with macular edema has
not been evaluated; potential benefits and risks for the individual
patient should be considered if deciding whether ZEPOSIA should be
discontinued
Posterior Reversible Encephalopathy Syndrome (PRES): Rare
cases of PRES have been reported in patients receiving a S1P
receptor modulator. If a ZEPOSIA-treated patient develops
unexpected neurological or psychiatric symptoms or any symptom/sign
suggestive of an increase in intracranial pressure, a complete
physical and neurological examination should be conducted. Symptoms
of PRES are usually reversible but may evolve into ischemic stroke
or cerebral hemorrhage. Delay in diagnosis and treatment may lead
to permanent neurological sequelae. If PRES is suspected, treatment
with ZEPOSIA should be discontinued
Unintended Additive Immunosuppressive Effects from Prior
Immunosuppressive or Immune-Modulating Drugs: When switching
from drugs with prolonged immune effects, the half-life and mode of
action of these drugs must be considered to avoid unintended
additive immunosuppressive effects while at the same time
minimizing risk of disease reactivation. Initiating treatment with
ZEPOSIA after treatment with alemtuzumab is not recommended
Severe Increase in Disability After Stopping ZEPOSIA:
Severe exacerbation of disease, including disease rebound, has been
rarely reported after discontinuation of a S1P receptor modulator.
The possibility of severe exacerbation of disease should be
considered after stopping ZEPOSIA treatment so patients should be
monitored upon discontinuation
Immune System Effects After Stopping ZEPOSIA: After
discontinuing ZEPOSIA, the median time for lymphocyte counts to
return to the normal range was 30 days with approximately 90% of
patients in the normal range within 3 months. Use of
immunosuppressants within this period may lead to an additive
effect on the immune system, therefore caution should be applied
when initiating other drugs 4 weeks after the last dose of
ZEPOSIA
Most common Adverse Reactions (≥ 4%): upper respiratory
infection, hepatic transaminase elevation, orthostatic hypotension,
urinary tract infection, back pain, and hypertension.
For additional safety information, please see the full
Prescribing Information and Medication Guide.
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 Zeposia (ozanimod) may not receive regulatory
approval for the additional indication described in this release in
the currently anticipated timeline or at all and, if approved,
whether it will be 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, 2019, 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.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20200602005291/en/
Bristol Myers Squibb
Media Inquiries: 609-252-3345 media@bms.com
Kirby Hosea Kirby.Hosea@bms.com
Investors: Tim Power 609-252-7509 Timothy.Power@bms.com
Nina Goworek 908-673-9711 Nina.Goworek@bms.com
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Aug 2024 to Sep 2024
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Sep 2023 to Sep 2024