CNSPulse
W119

EFFICACY AND SAFETY OF XANOMELINE/TROSPIUM CHLORIDE DURING TRANSITION FROM ATYPICAL ANTIPSYCHOTICS IN PARTICIPANTS WITH STABLE SCHIZOPHRENIA SYMPTOMS IN EMERGENT-5

Craig Chepke — Brooke Kempf2, James Appio3, Andrew Thorpe3, Gerard Zitnik3, Pierre Nicolas3, Rajiv Radhakrishnan3, Andrew J. Cutler4 1Excel Psychiatric Associates, 2Indiana University, 3Bristol-Myers Squibb, 4SUNY Upstate Medical University

2026 ASCP Annual Meeting

Introduction

Medication switching is common in schizophrenia; however, clinicians may be concerned about decompensation when switching medications in clinically stable adults. The most frequent reasons for switching antipsychotic (AP) medications may include adverse events (AEs) or a lack of efficacy. Xanomeline and trospium chloride (KarXT), approved by the US Food and Drug Administration for schizophrenia treatment, provides a novel mechanism of action, exerting effects through M1 and M4 muscarinic receptor agonism, which has the potential to reduce the AE burden associated with atypical APs. Previous results from EMERGENT-5 (NCT04820309) have demonstrated that KarXT was safe, with a trend toward symptom improvement over 1 year in clinically stable adults with schizophrenia who switched from a prior AP. This analysis evaluated symptom stability during the 2-week treatment transition period from a previous atypical AP to KarXT and safety following KarXT initiation in participants in the EMERGENT-5 trial.

Methods

EMERGENT-5 was a phase 3, 52-week, multicenter, outpatient, open-label trial in adults with schizophrenia with stable symptoms, no prior KarXT use, a Positive and Negative Syndrome Scale (PANSS) total score ≤80, and a Clinical Global Impression-Severity (CGI-S) score ≤4. Prior APs were washed out 2 weeks before or 5 half-lives between the screening and baseline visits. Participants initiated KarXT 50 mg/20 mg (xanomeline/trospium) twice daily and uptitrated to a maximum dose of 125 mg/30 mg (xanomeline/trospium) twice daily for 52 weeks. Outcomes assessed in this analysis included the change from screening to baseline in PANSS total, PANSS positive, and PANSS negative scores and the incidence of new-onset treatment emergent AEs (TEAEs) in the 8 weeks following KarXT initiation.

Results

Most participants (91.4%) had ≥1 prior AP, most commonly quetiapine (26.3%), risperidone (21.5%), aripiprazole (13.8%), and olanzapine (13.4%). The overall mean (standard deviation [SD]) washout duration was 6.0 (29.2) days. Mean (SD) PANSS total score change from screening to baseline was 0.3 (7.0); this change was similar between groups when stratifying by prior AP (quetiapine: 0.0; risperidone: 0.4; aripiprazole: −0.3; olanzapine: 0.0). The overall mean (SD) PANSS positive score change from screening to baseline was −0.3 (2.6); this change was similar between groups when stratifying by prior AP (quetiapine: −0.3; risperidone: −0.1; aripiprazole: −0.8; olanzapine: −0.2). The overall mean (SD) PANSS negative score change from screening to baseline was 0.3 (3.0); this change was similar between groups when stratifying by prior AP (quetiapine: 0.2; risperidone: 0.1; aripiprazole: 0.3; olanzapine: 0.7). KarXT was generally well tolerated and no new safety or tolerability issues emerged during the transition from prior AP to KarXT. Following KarXT initiation (weeks 1-8), the most common TEAEs were procholinergic and anticholinergic in nature: nausea (18.9%), vomiting (15.4%), and constipation (12.5%). Incidence rates for these new-onset AEs decreased over time.

Conclusions

Switching APs is common among individuals with schizophrenia. PANSS total, PANSS positive, and PANSS negative scores remained stable when transitioning participants from a previous atypical AP to KarXT, regardless of the prior AP used. Incidence rates for newonset TEAEs declined over time. These data suggest that stable individuals can be safely transitioned from previous APs to KarXT without destabilization of schizophrenia symptoms.