Adults With Schizophrenia Remain Stable When Transitioning from Atypical Antipsychotic to Cobenfy

Data presented at the 2026 Annual Congress of the Schizophrenia International Research Society show adult outpatients with schizophrenia remained stable when switching from an oral atypical antipsychotic to xanomeline/trospium chloride (Cobenfy; Bristol Myers Squibb).¹

What is Xanomeline/Trospium Chloride?

Xanomeline/trospium chloride (formerly KarXT) is an oral medication approved by the FDA for the treatment of schizophrenia in adults. Its safety and efficacy were demonstrated in the EMERGENT clinical trials—EMERGENT 1 (NCT03697252), EMERGENT 2 (NCT04659161), EMERGENT 3 (NCT04738123), EMERGENT 4 (NCT04659174), and EMERGENT 5 (NCT04820309)—as well as a phase 4 trial (NCT00232687) with slower titration to evaluate tolerability of administration with and without food.^1,2

Xanomeline, a dual M₁- and M₄-preferring muscarinic receptor agonist, is combined with trospium chloride, a muscarinic receptor antagonist that does not appreciably cross the blood-brain barrier, primarily confining its effects on peripheral tissues. The agent’s efficacy is thought to be due to the agonist activity of xanomeline at M₁ and M₄ muscarinic acetylcholine receptors in the central nervous system.²

“[Xanomeline/trospium chloride] represents a fundamentally different approach to treating schizophrenia as the first novel mechanism in decades, and physicians are naturally curious as to how they can switch and transition adult patients with schizophrenia to this innovative medication,” Harald Hampel, MD, PhD, senior vice president, worldwide head of neuroscience, global medical affairs, at Bristol Myers Squibb, said in a news release. “We carefully designed this trial with the scientific rigor and curiosity in mind, knowing that treatment decisions are not made lightly, and patient benefit, safety and stability is our ultimate goal.”²

Clinical Trial Information

Antipsychotic medications (APs) can cause significant side effects resulting in treatment discontinuation and relapse. Because xanomeline/trospium chloride does not block D2 dopamine receptors, it is believed that the therapy potentially lowers the risk of cardiometabolic and extrapyramidal adverse effects (AEs).¹

This 8-week, multicenter, randomized, open-label, outpatient trial assessed the efficacy and safety of a switch from an AP to xanomeline/trospium chloride monotherapy in adults aged 18 to 65 years with schizophrenia. Participants were randomly assigned to 1 of 2 treatment groups: a slower transition from an AP to xanomeline/trospium chloride over 4 weeks (25% reduction in original AP dose each week; n = 53) or a faster transition from AP to xanomeline/trospium chloride over 2 weeks (50% reduction in AP dose each week; n = 52). All enrolled patients adhered to the same titration schedule and were initiated at xanomeline/trospium chloride 50 mg/20 mg twice per day for 1 week, and then uptitrated to a target maintenance dosage of xanomeline/trospium chloride 125 mg/30 mg monotherapy over 8 weeks.¹

The trial’s primary end point was all-cause discontinuation of xanomeline/trospium chloride. Secondary end points included change from baseline to week 8 in Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), and Personal and Social Performance (PSP) scores. Secondary safety end points included xanomeline/trospium chloride AE-related discontinuations and AE incidence.¹

Patients Remain Stable When Treated With Xanomeline/Trospium Chloride

Approximately 86% of participants 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, respectively. There were no patients who discontinued because of lack of treatment efficacy; only 1 (1.9%) participant and 2 (3.8%) participants in the slower and faster transition groups, respectively, discontinued treatment early due to treatment-emergent AEs (TEAEs).¹

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, and the mean change in CGI-S score was –0.2 in both transition groups. From baseline to week 8, mean PSP scores increased by about 1.1 and 0.7 in the slower and faster transition groups, respectively.¹

The authors wrote that approximately 49% of participants had at least 1 TEAE, but importantly, none were serious. TEAE rates were consistent with those reported in pooled analyses of the EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials in participants with schizophrenia.¹

Both slower and faster transitions from atypical APs to xanomeline/trospium chloride monotherapy were generally safe and effective among enrolled participants with schizophrenia, suggesting that either a slower or faster transition method may be considered when patients switch treatment. The authors emphasize that these data may help health care professionals initiate novel-acting medications in patients with schizophrenia by providing them with evidence-based guidance on how to switch to xanomeline/trospium chloride from oral atypical APs.¹

“While transitioning patients is common in schizophrenia, clinicians have historically had limited data to help guide these decisions, especially for differentiated treatments like [xanomeline/trospium chloride],” said David Walling, PhD, principal investigator and chief clinical officer at Cenexel – CNS. “The data presented today provide much-needed insight into what happens during a switch to [xanomeline/trospium chloride], notably that patients remained stable through 8 weeks of treatment regardless of a slower or faster cross-titration, which will help health care professionals make informed treatment decisions for adults living with schizophrenia.”²

REFERENCES

1. Walling D, Marbot N, Shirikjian E, et al. Open-Label, Randomized Study to Assess Safety and Efficacy of Slow and Accelerated Switching to Xanomeline/Trospium from Standard of Care Atypical Antipsychotics in Participants with Schizophrenia. Presented at: Schizophrenia International Research Society (SIRS); Florence, Italy. March 25-29. Abstract S254.

2. Open Label Outpatient Switch Study Demonstrates Symptom Stability During Transition from Oral Atypical Antipsychotics to Cobenfy™ (xanomeline and trospium chloride). Bristol Myers Squibb. News release. March 28, 2026. Accessed June 5, 2026. https://investors.bms.com/iframes/press-releases/press-release-details/2026/Open-Label-Outpatient-Switch-Study-Demonstrates-Symptom-Stability-During-Transition-from-Oral-Atypical-Antipsychotics-to-Cobenfy-xanomeline-and-trospium-chloride/default.aspx