Bristol Myers Squibb Announces Data from Phase 4 Clinical Trial Evaluating Symptom Stability, Safety and Tolerability of Cobenfy (Xanomeline and Trospium Chloride)

Bristol Myers Squibb announced data from a Phase 4 clinical trial evaluating the symptom stability, safety and tolerability of Cobenfy (xanomeline and trospium chloride) when switching adult outpatients with schizophrenia from an oral atypical antipsychotic to Cobenfy monotherapy. Through 8 weeks, patients remained stable with mean Positive and Negative Syndrome Scale (PANSS) total scores remaining below baseline, and no new safety signals were observed, regardless of cross-titration duration. These findings provide important evidence to help inform treatment switch strategies in clinical practice.

Data were presented at the 2026 Annual Congress of the Schizophrenia International Research Society (SIRS) taking place March 25-29 in Florence, Italy. This 8-week, open-label trial evaluated two cross-titration strategies in adults with schizophrenia (n=105): tapering the existing atypical antipsychotic down over the faster 2 week (n=52) or slower 4 week (n=53) period while simultaneously up-titrating Cobenfy to the target dose of 125/30 mg BID, over two weeks in both arms. Patients were required to have a PANSS total score at or below 80 at screening and baseline, Clinical Global Impression-Severity (CGI-S) score of =4, and to be on a stable dose of an oral atypical antipsychotic for at least 6 weeks. The primary objective of the trial was to evaluate the rate of all-cause Cobenfy discontinuation over a period of 8 weeks.

Key secondary endpoints included Cobenfy discontinuation due to a lack of efficacy, incidence of, and discontinuations due to adverse events (AEs), change from baseline (CFB) to week 8 in the PANSS total score, CGI-S, Personal and Social Performance (PSP), and Medication Satisfaction Questionnaire (MSQ). In the trial, approximately 86% of patients completed 8 weeks of treatment, with discontinuation rates of 15.1% (n=8) and 13.5% (n=7) in the slower and faster transition groups. No patients discontinued treatment with Cobenfy due to lack of efficacy.

Mean changes in PANSS total scores from baseline to week 8 were -4.2 in the slower transition group and -3.1 in the faster transition group. Mean change in CGI-S scores was -0.2 in both the slower and faster transition groups. From baseline to week 8, mean PSP scores improved by 1.1 and 0.7 in the slower and faster transition groups, respectively.

Across both cross-titration groups, treatment with Cobenfy was generally well tolerated, with no new safety or tolerability issues emerging. In the trial, 49% of patients had =1 treatment-emergent adverse event (TEAE) and none were serious. TEAE rates were consistent with those reported in the EMERGENT trials.

In the slower and faster transition groups, 1 (1.9%) patient and 2 (3.8%) patients, respectively, discontinued treatment early due to TEAEs. 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 on 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. COBENFY (xanomeline and trospium chloride) is indicated for the treatment of schizophrenia in adults. 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, untreated narrow-angle glaucoma.

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. 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.

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. 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.

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. Angioedema of the face, lips, tongue, and/or larynx has been reported with COBENFY and trospium chloride, a component of COBENFY.