Cobenfy (xanomeline/trospium) / ZAI Lab, BMS, Royalty, PureTech - LARVOL DELTA

Commentary: Real-world effectiveness and safety of xanomeline and trospium for treatment-resistant schizophrenia in a state hospital system. (PubMed, Front Psychiatry) - No abstract available

Journal • Real-world evidence • CNS Disorders • Psychiatry • Schizophrenia

A Qualitative Investigation of the Experience of Taking Xanomeline and Trospium Chloride for Schizophrenia, Part 1: Perceived Impact on Symptoms. (PubMed, Schizophr Bull Open) - "These qualitative findings highlight xanomeline/trospium's potential to provide meaningful relief across multiple symptom domains and support functional recovery. A companion report explores quality of life and medication satisfaction."

Journal • CNS Disorders • Psychiatry • Schizophrenia

A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for the Treatment of Agitation Associated With Alzheimer's Disease (ADAGIO-1) (clinicaltrials.gov) - P3 | N=352 | Recruiting | Sponsor: Bristol-Myers Squibb

Trial initiation date • Alzheimer's Disease • CNS Disorders • Aβ42 • CSF Aβ42 • p-tau181

A Study to Assess Efficacy and Safety of KarXT for the Treatment of Psychosis Associated With Alzheimer's Disease (ADEPT-2) (clinicaltrials.gov) - P3 | N=500 | Active, not recruiting | Sponsor: Karuna Therapeutics | Trial completion date: Jul 2025 ➔ Dec 2026 | Trial primary completion date: Jul 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Psychiatry

A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3) (clinicaltrials.gov) - P3 | N=148 | Recruiting | Sponsor: Bristol-Myers Squibb | N=110 ➔ 148

Enrollment change • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3) (clinicaltrials.gov) - P3 | N=450 | Recruiting | Sponsor: Bristol-Myers Squibb

Trial initiation date • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-2) (clinicaltrials.gov) - P3 | N=274 | Recruiting | Sponsor: Bristol-Myers Squibb

Trial initiation date • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

KAR-013: A rollover study for subjects that complete KAR-012 trial, to assess Long-term Safety and Tolerability of Adjunctive KarXT in Subjects with Inadequately Controlled Symptoms of Schizophrenia (clinicaltrialsregister.eu) - P2/3 | N=50 | Completed | Sponsor: Karuna Therapeutics Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

BALSAM-1: A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (clinicaltrials.gov) - P3 | N=274 | Recruiting | Sponsor: Bristol-Myers Squibb

Trial initiation date • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

SHINE: A Study Evaluating the Efficacy of Xanomeline/Trospium (XT) on Cognitive Impairment After 24 and 52 Weeks of Treatment in Adult Participants With Schizophrenia (clinicaltrials.gov) - P3 | N=160 | Recruiting | Sponsor: European Group for Research In Schizophrenia

New P3 trial • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Low incidence of extrapyramidal symptoms following treatment with a muscarinic agonist medication for schizophrenia. (PubMed, Schizophr Res) - "Non-dopamine-focused medications like KarXT offer an effective, alternative treatment for schizophrenia with minimal EPS liability that may benefit individuals who require these medications."

Journal • CNS Disorders • Psychiatry • Schizophrenia • DRD2

SHINE: A Study Evaluating the Efficacy of Xanomeline/Trospium (XT) on Cognitive Impairment After 24 and 52 Weeks of Treatment in Adult Participants With Schizophrenia (clinicaltrials.gov) - P3 | N=171 | Recruiting | Sponsor: European Group for Research In Schizophrenia | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

CN012-0046: A Phase 3 Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine (clinicaltrialsregister.eu) - P2/3 | N=185 | Not yet recruiting | Sponsor: Bristol-Myers Squibb Services Unlimited Company

New P2/3 trial • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

Effectiveness and Adverse-effect Switch Evaluation of Xanomeline and Trospium Chloride (KarXT) (clinicaltrials.gov) - P=N/A | N=1500 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

Budget impact of xanomeline and trospium chloride for the treatment of adults with schizophrenia in the United States. (PubMed, J Manag Care Spec Pharm) - "Sensitivity and scenario analyses demonstrated minimal budget impact sensitivity to parameter variations, with results most sensitive to the cost of X/T and inputs used to estimate the size of the eligible patient population. The safety and tolerability profile of X/T, coupled with its minimal PMPM budget impact of $0.0177 in year 1 up to $0.1006 in year 3, based on market uptake of 1%, 2%, and 3% in years 1, 2, and 3, respectively, supports the inclusion of X/T on the formularies of third-party US health care plans for adults with schizophrenia."

HEOR • Journal • CNS Disorders • Metabolic Disorders • Movement Disorders • Psychiatry • Schizophrenia

SHINE: A Study Evaluating the Efficacy of Xanomeline/Trospium (XT) on Cognitive Impairment After 24 and 52 Weeks of Treatment in Adult Participants With Schizophrenia (clinicaltrials.gov) - P3 | N=127 | Recruiting | Sponsor: European Group for Research In Schizophrenia

New P3 trial • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

CN012-0024: A Phase 3 Study to Evaluate the Safety and Efficacy of KarXT + KarX-EC for thenTreatment of Agitation Associated with Alzheimers Disease. (clinicaltrialsregister.eu) - P2/3 | N=90 | Recruiting | Sponsor: Bristol-Myers Squibb Services Unlimited Company

New P2/3 trial • Alzheimer's Disease • CNS Disorders • Aβ42 • CSF Aβ42 • p-tau181

New Interventions for Schizophrenia: Navigating the Treatment Landscape. (PubMed, Span J Psychiatry Ment Health) - "In the past few years, schizophrenia drug development has re-accelerated, including the first US approval of a non-D2 antipsychotic mechanism (xanomeline-trospium), and several late-stage programmes aiming to treat symptom domains that matter most to long-term functioning...Successful translation requires alignment among biological targets, trial design, and patient phenotypes. In this review, we examine emerging interventions and propose a pragmatic translational framework centered on domain-specific prescribing, earlier implementation of measurement-based care, and biomarker-informed stratification."

Journal • CNS Disorders • Psychiatry • Schizophrenia • DRD2

A Study to Evaluate the Effects of Lithium, Valproic Acid, and Lamotrigine on the Pharmacokinetics of KarXT and Effects of KarXT on the Pharmacokinetics of Lithium, Valproic Acid, and Lamotrigine in Healthy Participants (clinicaltrials.gov) - P1 | N=133 | Completed | Sponsor: Karuna Therapeutics | Recruiting ➔ Completed

Trial completion

REAL-WORLD SAFETY OF XANOMELINE/TROSPIUM CHLORIDE IN SCHIZOPHRENIA MANAGEMENT (ISPOR 2026) - "Real-world safety profile of xanomeline/trospium chloride differed from risperidone. There was concordance between FAERS- and trial-reported AEs for xanomeline/trospium chloride. However, the FAERS analysis revealed additional AEs which were not detected the NLP analysis."

Clinical • Real-world • Real-world evidence • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Psychiatry • Schizophrenia

Comparative efficacy and tolerability of antidopaminergic and muscarinic antipsychotics for acute schizophrenia: a network meta-analysis of randomised controlled trials indexed in international English and Chinese databases. (PubMed, Lancet) - "This network meta-analysis provides evidence for small-to-medium clinically relevant differences between antipsychotics in efficacy; this finding warrants stronger and more specific emphasis in clinical guidelines. Nonetheless, important differences in tolerability need to be considered for individualised drug choice, with partial dopamine agonists having overall better tolerability and xanomeline-trospium lacking adverse effects of dopamine-blocking agents but resulting in cholinergic and anticholinergic adverse events. Future research should directly compare xanomeline-trospium with other antipsychotics to confirm its efficacy; modern trials using clozapine early in schizophrenia are needed to establish whether it improves outcomes and prevents chronification."

Journal • Retrospective data • CNS Disorders • Psychiatry • Schizophrenia

Xanomeline-Trospium Chloride as a New Paradigm in the Treatment of Schizophrenia Through Muscarinic Modulation: A Renewed Hope in Psychiatric Care. (PubMed, Cureus) - "Although xanomeline-trospium chloride is already approved for the treatment of schizophrenia, particularly for patients who need better metabolic and cognitive outcomes, future studies should aim to investigate its efficacy in treatment-resistant schizophrenia, early-stage intervention, and other neuropsychiatric disorders. This review aims to integrate the current evidence and assess the potential of xanomeline-trospium chloride as a novel therapeutic approach in the management of schizophrenia."

Journal • Review • CNS Disorders • Mental Retardation • Psychiatry • Schizophrenia

STRATEGIC COMPARISON OF CENTER FOR PHARMACOECONOMICS AND INSTITUTE FOR CLINICAL AND ECONOMIC REVIEW ECONOMIC EVALUATIONS (ISPOR 2026) - "OBJECTIVES: To characterize and compare economic evaluations of the same intervention by the Center for Pharmacoeconomics (CPE) and Institute for Clinical and Economic Review (ICER), focusing on model inputs and results. CPE and ICER assessments of acoramidis, xanomeline/trospium chloride, sacubitril/valsartan, and dimethyl fumarate were paired by intervention for data extraction into a pre-specified grid... CPE and ICER assessments yielded broadly consistent conclusions regarding value across interventions under a conventional cost-effectiveness framework. While input parameters varied between paired assessments, potentially reflecting differences in reporting practices, numerical concordance was relatively high where comparable parameters were available. These findings suggest that similar value conclusions may be reached despite heterogeneity between conventional CPE and ICER cost-effectiveness models."

Clinical • HEOR • Review

CN012-0037: A Phase 3 Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (clinicaltrialsregister.eu) - P2/3 | N=89 | Recruiting | Sponsor: Bristol-Myers Squibb Services Unlimited Company

New P2/3 trial • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry

CN012-0038: A Phase 3 Open-label Extension Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (clinicaltrialsregister.eu) - P2/3 | N=110 | Recruiting | Sponsor: Bristol-Myers Squibb Services Unlimited Company

New P2/3 trial • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry