Unique safety profile

with COBENFY

Demonstrated in over 1250 patients across 5 clinical trials1-7

Shield

No warnings or precautions for metabolic changes, including weight gain8

No warnings or precautions for any movement disorder8

No Boxed Warning8

COBENFY has warnings and precautions for8:

  • Risk of:
    • urinary retention
    • use in patients with hepatic impairment
    • use in patients with biliary disease
    • angioedema
    • use in patients with narrow-angle glaucoma
  • Decreased gastrointestinal motility
  • Increases in heart rate
  • Anticholinergic adverse reactions in patients with renal impairment
  • Central nervous system effects

DEMONSTRATED ACROSS CLINICAL TRIALS2,3

Overall discontinuation rates due to adverse reactions were similar between COBENFY (6%) and placebo (4%)8

Adverse Reactions Reported in ≥2% of COBENFY-Treated Patients and Greater Than Rate of Placebo in EMERGENT-2 & -38

Graph of adverse reactions reported in COBENFY-Treated Patients occurred at a greater rate than placebo in EMERGENT-2 & -3
a Dyspepsia includes dyspepsia and esophageal discomfort.8
b Hypertension includes hypertension, blood pressure increased, labile hypertension, and orthostatic hypertension.8
c Abdominal pain includes abdominal discomfort, abdominal pain upper, abdominal pain, abdominal pain lower, and abdominal tenderness.8
d Tachycardia includes tachycardia, heart rate increased, and sinus tachycardia.8
e Cough includes cough and productive cough.8
f EPS (non-akathisia) includes dyskinesia, drooling, dystonia, extrapyramidal disorder, muscle contraction involuntary, and muscle spasms.8

The majority of cholinergic adverse events were characterized as mild7

Proportion and Intensity of Cholinergic Adverse Events Reported in EMERGENT-2 & -37

Chart of the proportion and intensity of cholinergic adverse events reported in COBENFY-treated patients in EMERGENT-2 & -3

METABOLIC CHANGES WITH COBENFY7

Average Change From Baseline at Week 5 (pooled EMERGENT-1, -2, & -3) and Week 52 (pooled EMERGENT-4 & -5)5,7

Average metabolic change with Cobenfy from baseline at week 5 (pooled EMERGENT-1, -2, & -3) and week 52 (pooled EMERGENT-4 &-5)
* Data are exploratory from an ad hoc analysis and represent long-term data as of April 17, 2023.7
  AE=adverse event.

≤1% OF PATIENTS HAD MOVEMENT DISORDERS WITH COBENFY AT WEEK 527

Movement Disorders With COBENFY7
Pooled Data From Long-Term Trials (N=718)*

Graph of pooled data from long-term trials of the prevalence of movement disorders with Cobenfy

<1% of patients taking COBENFY discontinued treatment due to EPS.7

Chart of mean change across movement disorder scales with Cobenfy

Mean change across movement disorder scales (AIMS, BARS, SAS) was -0.2.7

AIMS=Abnormal Involuntary Movement Scale; BARS=Barnes Akathisia Rating Scale; EPS=extrapyramidal symptoms; SAS=Simpson Angus Scale; Wk=week.

 

~96% OF PATIENTS DID NOT EXPERIENCE CLINICALLY SIGNIFICANT WEIGHT GAIN9*

Weight Change Over the 52-Week Treatment Period (pooled data)9
EMERGENT -4 & -5

"Over the 52-week treatment period in EMERGENT -4 & -5, patients experienced an average weight loss of 4.7 lbs. while taking Cobenfy"
Chart of mean weight change from baseline while taking Cobenfy Chart of mean weight change from baseline while taking Cobenfy

« Swipe left for 52-week weight data

18% of patients taking Cobenfy had a decrease in body weight of ≥7%. 4% of patients had an increase in body weight of ≥7%.
* Defined as ≥7% increase in body weight.9

WELL STUDIED ACROSS SHORT- AND LONG-TERM TRIALS, UP TO 52 WEEKS7

Select Pooled Adverse Reactions in >2% of Patients From Phase 3 Short- and Long-Term Trials7,8

Graph of pooled adverse reactions in >2% of patients from phase 3 short- and long-term trials of Cobenfy

Additional pooled adverse reactions in short- or long-term trials with rates ≥2% and <5%: anxiety (3%, 3%); vision blurred (3%, 2%); hyperhidrosis (2%, 4%); weight increased (2%, 3%); salivary hypersecretion (2%, 3%); akathisia (2%, 1%); coughe (2%, 2%); extrapyramidal symptoms (EPS), non-akathisiaf (2%, 1%); orthostatic hypotension (2%, 1%); agitation (2%, <1%); back pain (1%, 4%); upper respiratory tract infection (<1%, 3%); urinary tract infection (<1%, 3%); decreased appetite (<1%, 2%); urinary retention (<1%, 2%).

In long-term trials, TEAEs were primarily mild to moderate (96%).7

a Dyspepsia includes dyspepsia and esophageal discomfort.8
b Hypertension includes hypertension, blood pressure increased, labile hypertension, and orthostatic hypertension.8
c Abdominal pain includes abdominal discomfort, abdominal pain upper, abdominal pain, abdominal pain lower, and abdominal tenderness.8
d Tachycardia includes tachycardia, heart rate increased, and sinus tachycardia.8
e Cough includes cough and productive cough.8
f EPS (non-akathisia) includes dyskinesia, drooling, dystonia, extrapyramidal disorder, muscle contraction involuntary, and muscle spasms.8

 

* Data are exploratory from an ad hoc analysis and represent long-term data as of April 17, 2023.
  Safety population defined as all participants who received ≥1 dose of trial medication.7
  GERD=gastroesophageal reflux disease; TEAE=treatment-emergent adverse event.

5-Week Trial Designs

EMERGENT-1, -2, and -3 were three pivotal, 5-week, placebo-controlled studies evaluated mean change in PANSS total score in adult patients with schizophrenia experiencing acute psychosis.1,2,4,5

EMERGENT-2 & -3 were phase 3 trials, and EMERGENT-1 was a phase 2 trial.1,2,5

See additional study design details.

52-Week Trial Designs5,6

EMERGENT-4 was a 52-week, open-label, extension trial in people who completed the treatment period of the 5-week, randomized, double-blind, placebo-controlled EMERGENT-21 and EMERGENT-32 trials (N=152).5

EMERGENT-5 was a phase 3, multicenter, outpatient, 52-week, open-label trial in adults with a confirmed diagnosis of schizophrenia who have stable symptoms of schizophrenia and have had no prior exposure to xanomeline/trospium; participants with a Positive and Negative Syndrome Scale (PANSS) total score ≤80 and a Clinical Global Impression–Severity (CGI-S) score ≤4 were eligible.6

See additional study design details.

 

References: 

  1. Kaul I, Sawchak S, Correll CU, et al. Efficacy and safety of the muscarinic receptor agonist KarXT (xanomeline-trospium) in schizophrenia (EMERGENT-2) in the USA: results from a randomised, double-blind, placebo-controlled, flexible-dose phase 3 trial. Lancet. 2024;403(10422):160-170.
  2. Kaul I, Sawchak S, Walling DP, et al. Efficacy and safety of xanomeline-trospium chloride in schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2024;81(8):749-756.
  3. Kaul I, Sawchak S, Claxton A, et al. Efficacy of xanomeline and trospium chloride in schizophrenia: pooled results from three 5-week, randomized, double-blind, placebo-controlled, EMERGENT trials. Schizophrenia (Heidelb). 2024;10(1):102.
  4. Brannan SK, Sawchak S, Miller AC, Lieberman JA, Paul SM, Breier A. Muscarinic cholinergic receptor agonist and peripheral antagonist for schizophrenia. N Engl J Med. 2021;384(8):717-726.
  5. Kaul I, Claxton A, Sauder C, et al. Long-term safety and efficacy of xanomeline and trospium chloride in schizophrenia: results from the 52-week, open-label EMERGENT-4 trial. Poster presented at: Psych Congress; October 29-November 2, 2024; Boston, MA.
  6. Kaul I, Claxton A, Sauder C, et al. 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 presented at: Psych Congress; October 29-November 2, 2024; Boston, MA.
  7. Data on file. Karuna Therapeutics, Inc., a Bristol Myers Squibb company; Boston, MA.
  8. COBENFY. Prescribing Information. Bristol-Myers Squibb Company; 2024.
  9. Kaul I, Brannan SK, Sawchak S, et al. Long-term safety of xanomeline and trospium chloride: pooled results from the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials. Poster presented at: The 2025 Annual Congress of the Schizophrenia International Research Society; March 29-April 2, 2025; Chicago, IL.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

COBENFY™ is contraindicated in patients with: urinary retention; moderate or severe (Child-Pugh Class B or C) hepatic impairment; gastric retention; history of hypersensitivity to COBENFY or trospium chloride—angioedema has been reported with COBENFY and trospium chloride; and 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

Pregnancy and Lactation: There is a pregnancy exposure registry that monitors outcomes in women exposed to psychiatric medications, including COBENFY, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling 1-866-961-2388 or visiting https://womensmentalhealth.org/research/pregnancyregistry/atypicalantipsychotic/.

There are no available data on COBENFY use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Additionally, there are no data on the presence of xanomeline or trospium in human milk, the effects on the breastfed infant, or the effects on milk production. However, xanomeline and trospium are present in animal milk, suggesting they may also be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for COBENFY and any potential adverse effects on the breastfed infant from COBENFY or the underlying maternal condition.

COBENFY (xanomeline and trospium chloride) is available in 50mg/20mg, 100mg/20mg, and 125mg/30mg capsules.

INDICATION

COBENFY™ (xanomeline and trospium chloride) is indicated for the treatment of schizophrenia in adults.

Please see U.S. Full Prescribing Information, including Patient Information.

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Cobenfy, Cobenfy Cares, and the Cobenfy logo are trademarks of Karuna Therapeutics, Inc., a Bristol Myers Squibb company.
© 2025 Bristol-Myers Squibb Company.

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