Long-term treatment with COBENFY was
associated with continued improvements in symptoms of
schizophrenia, demonstrating maintenance of effect
COBENFY was generally well tolerated over 52
weeks with a side effect profile consistent with prior trials of
COBENFY in schizophrenia
In-trial qualitative interviews found that a
majority of participants treated with COBENFY in the long-term
EMERGENT-5 trial reported Quality of Life improvements across
physical, social, emotional, and role functioning
Bristol Myers Squibb (NYSE: BMY) today announced new topline
results from the Phase 3 EMERGENT-4 and EMERGENT-5 open-label
trials evaluating the long-term efficacy, safety, and tolerability
of COBENFY™ (xanomeline and trospium chloride) in adults with
schizophrenia over 52 weeks of treatment. Data were presented at
the 2024 Psych Congress, taking place from October 29 – November 2,
2024 in Boston, MA.
“The results from our long-term trials further support the
differentiated profile of COBENFY and reinforce prior findings of
robust and maintained symptom reduction with long-term treatment,”
said Alyssa Johnsen, MD, PhD, senior vice president and head of
clinical development, Immunology, Cardiovascular and Neuroscience,
Bristol Myers Squibb. “We’re pleased to see a compelling safety and
tolerability profile associated with long-term COBENFY treatment
that is consistent with prior studies. Additionally, we continue to
see a lack of weight gain, movement disorders, or metabolic changes
with long-term use, reiterating the distinct profile and unique
mechanism of action of COBENFY. With COBENFY now available for
adults with schizophrenia, we look forward to further understanding
the real-world impact of this differentiated treatment option.”
Long-Term Safety and Efficacy of Xanomeline and Trospium
Chloride in Schizophrenia: Results From the 52-Week, Open-Label
EMERGENT-4 Trial (Poster 65)
EMERGENT-4 was a Phase 3, 52-week, outpatient, open-label
extension study evaluating the long-term safety, tolerability, and
efficacy of COBENFY in 156 adults with schizophrenia who previously
completed the treatment period of one of the Phase 3, five-week,
double-blind, placebo-controlled, efficacy and safety studies,
EMERGENT-2 or EMERGENT-3.
In the trial, treatment with COBENFY led to continued
improvements in symptoms of schizophrenia across all efficacy
measures, including the Positive and Negative Syndrome Scale
(PANSS) total, Clinical Global Impression-Severity (CGI-S), PANSS
positive subscale, and PANSS negative subscale scores, over 52
weeks. Participants who received placebo in the acute trials
demonstrated rapid improvement in symptoms once COBENFY was
initiated. At four weeks, PANSS total scores were comparable
between those who previously received COBENFY or placebo in the
acute trials. Improvements in symptoms of schizophrenia continued
throughout the 52-week study regardless of whether participants
received COBENFY or placebo in the acute trials. At the end of the
trial, 69% of participants who completed the study achieved ≥30%
improvement in schizophrenia symptoms from acute trial baseline, as
measured by the PANSS total score.
Long-term treatment with COBENFY was generally well-tolerated,
with no new safety or tolerability issues identified from prior
trials of COBENFY. The most common treatment-related
treatment-emergent adverse events, or TEAEs, (≥5%) were nausea,
vomiting, dyspepsia, dry mouth, and hypertension. The majority were
mild to moderate in intensity, did not lead to discontinuation of
COBENFY, and resolved with continued treatment. The discontinuation
rate due to TEAEs in EMERGENT-4 was 11%.
COBENFY was associated with a mean change in body weight of -1.9
kg (±4.7 kg) when measured from the acute trial baseline at 52
weeks. Additionally, COBENFY was not associated with clinically
meaningful changes in mean prolactin levels or on movement disorder
scale scores over 52 weeks. There were no reported TEAEs of
akathisia or tardive dyskinesia.
Long-Term Safety, Tolerability, and Efficacy of Xanomeline
and Trospium Chloride in People with Schizophrenia: Results From
the 52-Week, Open-Label EMERGENT-5 Trial (Poster 67)
EMERGENT-5 was a Phase 3, 52-week, outpatient, open-label study
evaluating the long-term safety, tolerability, and efficacy of
COBENFY in 566 adults in the U.S. with schizophrenia who had stable
symptoms on a prior antipsychotic and no prior exposure to COBENFY.
The trial enrolled participants with a PANSS total score ≤80 (mean
66.0) and a CGI-S score ≤4 (mean 3.4), who were considered mild to
moderately ill.
Treatment with COBENFY led to improvements in symptoms of
schizophrenia across all efficacy measures, including the PANSS
total, CGI-S, PANSS positive subscale, and PANSS negative subscale
scores at 52 weeks, confirming maintenance of effect with long-term
treatment. At week 52, 30% of participants had a ≥30% reduction
from baseline in the PANSS total score, with an average reduction
of -5.5-points from baseline.
Long-term treatment with COBENFY was generally well tolerated,
with no new safety or tolerability issues emerging. The most common
treatment-related TEAEs, (≥5%) were nausea, vomiting, constipation,
dry mouth, diarrhea, dyspepsia, dizziness, hypertension, and
somnolence. The majority of TEAEs were mild or moderate in
intensity and did not lead to discontinuation of COBENFY. In
EMERGENT-5, the discontinuation rate due to TEAEs was 18%.
Treatment with COBENFY was associated with a mean change in body
weight of -2.2 kg (+6.3 kg) from
baseline at 52 weeks. Additionally, COBENFY was not associated with
clinically meaningful changes in movement disorder scales or
hyperprolactinemia.
Participant Reported Insights from EMERGENT-5 In-Trial
Interviews (Poster 195 and Poster 196)
In EMERGENT-5, a qualitative interview-based survey was
administered to participants to characterize the self-reported
patient experience and perceived changes in Quality of Life (QoL)
when taking COBENFY. In the qualitative sub study, interviews were
conducted at six weeks (T1; N=70) and six months (T2; N=47) after
initiating treatment with COBENFY.
At study entry, most participants reported experiencing negative
QoL impacts in the four assessed domains, including physical,
social, emotional, and role functioning. Most participants
described improvements in their QoL in at least one domain within
six weeks of COBENFY treatment (86% improved, 13% unchanged, and 1%
worsened).
At six weeks, most participants described experiencing a high
level of satisfaction with COBENFY as compared to their prior
antipsychotic treatment, which was sustained for up to six months
of treatment. Participants also perceived improvements in symptoms
of schizophrenia and QoL while reporting little burden associated
with treatment as important contributors to their satisfaction. At
six months, nearly all participants (93%) indicated that they would
recommend COBENFY to a friend of family member, and 78% reported
that they would continue COBENFY after the trial if given the
option.
About Schizophrenia
Schizophrenia is a persistent and often disabling mental illness
impacting how a person thinks, feels and behaves. There are three
symptom domains of schizophrenia, which include positive symptoms
(e.g., hallucinations, delusions, disordered thinking and speech),
negative symptoms (e.g., lack of motivation, lack of emotional
expression/flat affect, social withdrawal) and cognitive
dysfunction (e.g., impaired attention, deficits in memory,
concentration and decision-making). The symptoms of schizophrenia
can affect all areas of people’s lives, making it difficult to
maintain employment, live independently and manage relationships.
Schizophrenia affects nearly 24 million people worldwide, including
2.8 million people in the United States, and is one of the top 15
leading causes of disability worldwide.
About COBENFY™ (xanomeline and trospium chloride)
COBENFY™ (xanomeline and trospium chloride), formerly KarXT, is
an oral medication for the treatment of schizophrenia in adults.
COBENFY combines xanomeline, a dual M1- and M4-preferring
muscarinic receptor agonist, with trospium chloride, a muscarinic
receptor antagonist that does not appreciably cross the blood-brain
barrier, primarily confining its effects to peripheral tissues.
While the exact mechanism of action of COBENFY is unknown, its
efficacy is thought to be due to the agonist activity of xanomeline
at M1 and M4 muscarinic acetylcholine receptors in the central
nervous system.
INDICATION
COBENFY™ (xanomeline and trospium chloride) is indicated for the
treatment of schizophrenia in adults.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
COBENFY is contraindicated in patients with:
- urinary retention
- moderate (Child-Pugh Class B) or severe (Child-Pugh Class C)
hepatic impairment
- gastric retention
- history of hypersensitivity to COBENFY or trospium chloride.
Angioedema has been reported with COBENFY and trospium
chloride.
- untreated narrow-angle glaucoma
WARNINGS AND PRECAUTIONS
Risk of Urinary Retention: COBENFY can cause urinary
retention. Geriatric patients and patients with clinically
significant bladder outlet obstruction and incomplete bladder
emptying (e.g., patients with benign prostatic hyperplasia (BPH),
diabetic cystopathy) may be at increased risk of urinary
retention.
COBENFY is contraindicated in patients with pre-existing urinary
retention and is not recommended in patients with moderate or
severe renal impairment.
In patients taking COBENFY, monitor for symptoms of urinary
retention, including urinary hesitancy, weak stream, incomplete
bladder emptying, and dysuria. Instruct patients to be aware of the
risk and promptly report symptoms of urinary retention to their
healthcare provider. Urinary retention is a known risk factor for
urinary tract infections. In patients with symptoms of urinary
retention, consider reducing the dose of COBENFY, discontinuing
COBENFY, or referring patients for urologic evaluation as
clinically indicated.
Risk of Use in Patients with Hepatic Impairment: Patients
with hepatic impairment have higher systemic exposures of
xanomeline, a component of COBENFY, compared to patients with
normal hepatic function, which may result in increased incidence of
COBENFY-related adverse reactions.
COBENFY is contraindicated in patients with moderate or severe
hepatic impairment. COBENFY is not recommended in patients with
mild hepatic impairment.
Assess liver enzymes prior to initiating COBENFY and as
clinically indicated during treatment.
Risk of Use in Patients with Biliary Disease: In clinical
studies with COBENFY, transient increases in liver enzymes with
rapid decline occurred, consistent with transient biliary
obstruction due to biliary contraction and possible gallstone
passage.
COBENFY is not recommended for patients with active biliary
disease such as symptomatic gallstones. Assess liver enzymes and
bilirubin prior to initiating COBENFY and as clinically indicated
during treatment. The occurrence of symptoms such as dyspepsia,
nausea, vomiting, or upper abdominal pain should prompt assessment
for gallbladder disorders, biliary disorders, and pancreatitis, as
clinically indicated.
Discontinue COBENFY in the presence of signs or symptoms of
substantial liver injury such as jaundice, pruritus, or alanine
aminotransferase levels more than five times the upper limit of
normal or five times baseline values.
Decreased Gastrointestinal Motility: COBENFY contains
trospium chloride. Trospium chloride, like other antimuscarinic
agents, may decrease gastrointestinal motility. Administer COBENFY
with caution in patients with gastrointestinal obstructive
disorders because of the risk of gastric retention. Use COBENFY
with caution in patients with conditions such as ulcerative
colitis, intestinal atony, and myasthenia gravis.
Risk of Angioedema: Angioedema of the face, lips, tongue,
and/or larynx has been reported with COBENFY and trospium chloride,
a component of COBENFY. In one case, angioedema occurred after the
first dose of trospium chloride. Angioedema associated with upper
airway swelling may be life-threatening. If involvement of the
tongue, hypopharynx, or larynx occurs, discontinue COBENFY and
initiate appropriate therapy and/or measures necessary to ensure a
patent airway. COBENFY is contraindicated in patients with a
history of hypersensitivity to trospium chloride.
Risk of Use in Patients with Narrow-angle Glaucoma:
Pupillary dilation may occur due to the anticholinergic effects of
COBENFY. This may trigger an acute angle closure attack in patients
with anatomically narrow angles. In patients known to have
anatomically narrow angles, COBENFY should only be used if the
potential benefits outweigh the risks and with careful
monitoring.
Increases in Heart Rate: COBENFY can increase heart rate.
Assess heart rate at baseline and as clinically indicated during
treatment with COBENFY.
Anticholinergic Adverse Reactions in Patients with Renal
Impairment: Trospium chloride, a component of COBENFY, is
substantially excreted by the kidney. COBENFY is not recommended in
patients with moderate or severe renal impairment (estimated
glomerular filtration rate (eGFR) <60 mL/min). Systemic exposure
of trospium chloride is higher in patients with moderate and severe
renal impairment. Therefore, anticholinergic adverse reactions
(including dry mouth, constipation, dyspepsia, urinary tract
infection, and urinary retention) are expected to be greater in
patients with moderate and severe renal impairment.
Central Nervous System Effects: Trospium chloride, a
component of COBENFY, is associated with anticholinergic central
nervous system (CNS) effects. A variety of CNS anticholinergic
effects have been reported with trospium chloride, including
dizziness, confusion, hallucinations, and somnolence. Monitor
patients for signs of anticholinergic CNS effects, particularly
after beginning treatment or increasing the dose. Advise patients
not to drive or operate heavy machinery until they know how COBENFY
affects them. If a patient experiences anticholinergic CNS effects,
consider dose reduction or drug discontinuation.
Most Common Adverse Reactions (≥5% and at least twice
placebo): nausea, dyspepsia, constipation, vomiting,
hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and
gastroesophageal reflux disease.
Use in Specific Populations:
- Moderate or Severe Renal Impairment: Not recommended
- Mild Hepatic Impairment: Not recommended
COBENFY (xanomeline and trospium chloride) is available in
50mg/20mg, 100mg/20mg, and 125mg/30mg capsules.
Please see U.S. Full Prescribing Information,
including Patient Information.
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, X, YouTube, Facebook and Instagram.
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 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 may not be consistent with the results to
date and that COBENFY (xanomeline and trospium chloride) may not
achieve its primary study endpoints or receive regulatory approval
for the indications described in this release in the currently
anticipated timeline or at all, any marketing approvals, if
granted, may have significant limitations on their use, and, if
approved, whether COBENFY for such indications 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, 2023, 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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