Switching to Cobenfy: Data Insights at SIRS from Harald Hampel, MD, PhD, MSc

New data on switching to Cobenfy (xanomeline trospium chloride) from atypical antipsychotics was shared at the recent Schizophrenia International Research Society meeting, providing clinically relevant insights.^1,2 Cross-titration at different durations showed no new safety concerns or discontinuation due to inefficacy, with low overall discontinuation rates.² Informed treatment switching strategy for patients with schizophrenia is a necessity, and expert Harald Hampel, MD, PhD, MSc, shares more here.

Psychiatric Times: What are the key details from recent data on the switch from atypical antipsychotics to Cobenfy monotherapy?

Harald Hampel, MD, PhD, MSc: Our phase 4 clinical trial evaluated the symptom stability, safety, and tolerability of Cobenfy when switching adult outpatients with schizophrenia from an oral atypical antipsychotic to Cobenfy monotherapy. Through 8 weeks of treatment, patients in the trial 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 (measured in both a faster 2-week and slower 4-week cross-titration). The primary outcome measured in the trial was all-cause discontinuation of Cobenfy, and approximately 86% of patients completed 8 weeks of treatment. The overall discontinuation rate was 14.3% (n=15), with discontinuation rates of 15.1% (n=8) and 13.5% (n=7) in the slower and faster transition groups (4 weeks vs 2 weeks), respectively.

Key secondary endpoints included Cobenfy discontinuation due to a lack of efficacy, incidence of and discontinuation due to adverse events, change from baseline to week 8 in the PANSS total score, Clinical Global Impression-Severity score (CGI-S), Personal and Social Performance (PSP), and Medication Satisfaction Questionnaire. No patients discontinued treatment with Cobenfy due to lack of efficacy. Mean change in PANSS total scores from baseline to week 8 was −4.2 points in the slower transition group and −3.1 points in the faster transition group. Mean change in CGI-S scores was −0.2 points in both the slower and faster transition groups. From baseline to week 8, mean PSP scores improved by 1.1 and 0.7 points 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 or more treatment-emergent adverse event (TEAE) and none were serious. TEAE rates were consistent with those reported in the EMERGENT trials.³ In the slower and faster transition groups, 1 (1.9%) patient and 2 (3.8%) patients, respectively, discontinued treatment early due to TEAEs.

PT: Why is data on switching to Cobenfy important for clinicians? Why are titration and informed medication switching essential generally?

Hampel: For patients suffering from symptoms of schizophrenia, treatment is not a one-size-fits-all approach and therefore switching treatments is common. Historically, clinicians have had limited data to help guide these decisions. Cobenfy represents a fundamentally different approach to treating schizophrenia as the first novel mechanism (targeting the cholinergic system) in decades, and physicians are naturally curious as to how they can transition adult patients with schizophrenia to benefit from the innovative mechanism of action and medication.

We carefully designed this trial, knowing that treatment decisions are not made lightly, and with patient benefit, safety and stability in mind. The switch trial provides descriptive safety and efficacy data on switching from stable doses of a prior antipsychotic to Cobenfy and shows that both the 2-week and 4-week treatment transition strategies were generally safe and maintained clinical stability in adults with schizophrenia.

PT: Why is it important to demonstrate the long-term clinical benefit and safety of Cobenfy?

Hampel: Schizophrenia is a complex, chronic, disabling condition that requires long-term management. For this reason, it is important for clinicians to feel confident that the treatments they prescribe show continued benefit and safety over time. The long-term data from our EMERGENT-4 and EMERGENT-5 trials provide evidence of the sustained, durable efficacy of Cobenfy and offer reassurance in its continued safety and tolerability.

PT: How do the potential adverse effects of Cobenfy differ from adverse effects often seen in traditional antipsychotics?

Hampel: While there have been no head-to-head trials conducted, the safety and tolerability profile of Cobenfy has been established across acute and long-term trials as part of the EMERGENT program. The most common adverse reactions (above 5% and at least double placebo group) included nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease. Across acute and long-term trials, Cobenfy had a low incidence of weight gain, metabolic changes, and movement disorders. Cobenfy does not have atypical antipsychotic class warnings or precautions and does not have a boxed warning.

Dr Hampel is senior vice president and worldwide head of medical affairs, neuroscience at Bristol Myers Squibb.

References

1. Abstract book: 2026 annual congress of the Schizophrenia International Research Society. Schizophrenia International Research Society. March 2026. Accessed April 27, 2026. https://schizophreniaresearchsociety.org/wp-content/uploads/2026/03/2026-SIRS-Abstract-Book.pdf

2. Open label outpatient switch study demonstrates symptom stability during transition from oral atypical antipsychotics to Cobenfy (xanomeline and trospium chloride). Press release. March 28, 2026. Accessed April 27, 2026. https://news.bms.com/news/details/2026/Open-Label-Outpatient-Switch-Study-Demonstrates-Symptom-Stability-During-Transition-from-Oral-Atypical-Antipsychotics-to-Cobenfy-xanomeline-and-trospium-chloride/default.aspx

3. Bukhari SMR, Btool S, Abbas J, et al. Cobenfy (xanomeline-trospium): a breakthrough FDA-approved therapy redefining schizophrenia treatment. Ann Med Surg (Lond). 2025;87(6):3065-3067.