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

Clinical Effects of Recently Developed Antipsychotic Drugs in Schizophrenia. (PubMed, Cent Nerv Syst Agents Med Chem) - "Promising new antipsychotic drugs include cariprazine, brexpiprazole, lumateperone, ulotaront, and xanomeline combined with trospium. Phase 3 clinical studies have shown therapeutic effects superior to those achieved with second-generation antipsychotic drugs."

Journal • CNS Disorders • Psychiatry • Schizophrenia

A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Schizophrenia in Adolescents (clinicaltrials.gov) - P3 | N=166 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

New Pharmacological Treatment Approaches for Schizophrenia: Navigating the Post-iclepertin Landscape. (PubMed, CNS Drugs) - "The most compelling therapeutic approaches continue to be serotonin-dopamine activity modulators (brilaroxazine) and emerging M4 selective agonists (NBI-1117568). While iclepertin's discontinuation represents a significant setback for GlyT1 inhibition strategies, the approval of KarXT and advancing pipeline candidates offer potential for therapeutic advances. Critical challenges include escalating placebo responses that compromise trial assay sensitivity, underscoring the need for improved patient stratification, refined trial methodology, and outcome measures that accurately capture real-world benefit."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Mental Retardation • Psychiatry • Schizophrenia • DRD2

Long-Term Safety and Efficacy of Xanomeline and Trospium Chloride in Schizophrenia: A 52-Week Open-Label Extension Trial. (PubMed, Am J Psychiatry) - "Similar patterns of continued improvement were observed for scores on the CGI-S, PANSS positive subscale, and PANSS negative subscale. Long-term treatment with X/T over 52 weeks was safe, generally well tolerated, and associated with durable symptom improvement in people with schizophrenia."

Clinical • Journal • CNS Disorders • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Psychiatry • Schizophrenia • Xerostomia

Targeting muscarinic receptors for treating schizophrenia. (PubMed, Neurotherapeutics) - "Current and future efforts are now focused on developing more selective orthosteric and allosteric mAChR agonists and more precisely characterizing their therapeutic activity (efficacy and safety) in clinical trials. These advances highlight mAChR pharmacology as a novel and clinically validated strategy that extends beyond dopamine D2 receptor antagonism to potentially address the full spectrum of schizophrenia symptoms."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

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

Adverse events • New trial • CNS Disorders • Psychiatry • Schizophrenia

From schizophrenia to dementia: Is Cobenfy a potential treatment for behavioral and psychological symptoms of dementia? (PubMed, J Int Med Res) - "Cobenfy, a novel combination of xanomeline and trospium chloride, has shown efficacy in schizophrenia and presents a promising alternative for treating behavioral and psychological symptoms of dementia...Cobenfy may offer a safer pharmacologic option for behavioral and psychological symptoms of dementia compared with existing treatments. Further research in older adult populations is warranted."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Psychiatry • Schizophrenia

Xanomeline-Trospium for the Treatment of Schizophrenia. (PubMed, Focus (Am Psychiatr Publ)) - "A search was conducted of all publicly available information (including press releases) and specifically within the databases MEDLINE, Embase, and PsycINFO, from their inception to May 1, 2025, noting the keywords "muscarinic," "schizophrenia," "xanomeline," and "emraclidine." A first-in-class medication approved for the treatment of schizophrenia in adults, XT possesses no direct action on dopamine D2 receptors. Post hoc analyses from the acute schizophrenia trials also indicate an impact on cognition among individuals with more significant baseline levels of cognitive impairment. Preliminary results of the adjunctive trial for adults with schizophrenia who are partial responders to other antipsychotics were not statistically significant, but ongoing studies are exploring XT for dementia-related psychosis and pediatric indications."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Movement Disorders • Pediatrics • Psychiatry • Schizophrenia • DRD2

A Study to Evaluate the Effect of KarXT on Urological Safety (clinicaltrials.gov) - P4 | N=60 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Psychiatry • Schizophrenia

KarXT Concentrations in the Breast Milk and Plasma of Lactating Females (clinicaltrials.gov) - P4 | N=8 | Recruiting | Sponsor: Karuna Therapeutics | Not yet recruiting ➔ Recruiting | Initiation date: Apr 2026 ➔ Jan 2026

Enrollment open • Trial initiation date

A Study of KarXT + KarX-EC for Treatment of Irritability in Children and Adolescents With Autism (clinicaltrials.gov) - P3 | N=176 | Not yet recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Jul 2026 ➔ Jul 2029 | Trial primary completion date: Jul 2026 ➔ Jul 2029

Trial completion date • Trial primary completion date • Autism Spectrum Disorder • Genetic Disorders

Exploring Adjunctive Novel Therapeutic Approach of KarXT (Xanomeline-Trospium Chloride) for Managing Psychotic Symptoms in Patients With Schizophrenia and Alzheimer's Disease. (PubMed, Brain Behav) - "Psychosis is a common feature of schizophrenia and AD, most often caused by high concentrations of dopamine in the brain, characterized by hallucinations, delusions, and disorganized thinking, resulting in markedly reduced quality of life for the patient and associated caregiver. Conventional treatments targeting dopamine receptors produce extrapyramidal symptoms and metabolic side effects, leading to noncompliance with medication. KarXT, with its dual action on M1 and M4 receptors and mAChR antagonism, greatly helps reduce the severity of the positive and negative symptoms. The side effects experienced were minimal and did not account for the discontinuation of treatment.An overview of the mechanism of action, clinical trials, and classical findings of KarXT for the management of psychotic symptoms in patients with schizophrenia and alzheimer's disease."

Journal • Review • Alzheimer's Disease • CNS Disorders • Psychiatry • Schizophrenia

Emerging Innovations in Third- and Fourth-Generation Antipsychotics: Mechanistic Advances and Clinical Implications. (PubMed, Psychopharmacol Bull) - "These emerging agents hold promise for better overall patient outcomes. This review highlights the clinical relevance of third- and fourth-generation antipsychotics and supports the growing trend toward targeted, receptor-specific treatments in managing psychotic disorders."

Journal • Review • CNS Disorders • Cognitive Disorders • Movement Disorders • Psychiatry • Schizophrenia

Novel drug treatments for schizophrenia. (PubMed, Nat Rev Drug Discov) - "The recent approval of the M1/M4 muscarinic acetylcholine receptor agonist xanomeline/trospium chloride has begun to expand the therapeutic toolbox for schizophrenia. This Review covers promising drug targets for schizophrenia treatment that impact neurotransmitter systems, immune processes and inflammation. Despite failed clinical trials of some agents with novel mechanisms, several have recently been shown to improve one or more symptom domains of schizophrenia, suggesting that these targets may lead to more effective treatments."

Journal • Review • Cardiovascular • CNS Disorders • Cognitive Disorders • Inflammation • Psychiatry • Schizophrenia • DRD2

A Study to Evaluate the Long-term Efficacy and Safety of KarXT + KarX-EC for Agitation in Alzheimer's Disease (ADAGIO-3) (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders

Long-term efficacy, safety, and tolerability of xanomeline and trospium chloride in schizophrenia: A 52-week, open-label trial (EMERGENT-5). (PubMed, Schizophr Res) - P3 | "Psychiatrically stable adults with schizophrenia were safely switched from prior antipsychotics to KarXT with a trend toward symptom improvement over 1 year. The safety and tolerability profile of KarXT was consistent with observations in prior clinical trials; no new safety issues emerged."

Clinical • Journal • Cardiovascular • CNS Disorders • Constipation • Dermatology • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Hypertension • Pain • Psychiatry • Schizophrenia • Xerostomia • DRD2

Drug Development. (PubMed, Alzheimers Dement) - "SUVN-L3307032 has the potential to be a new therapeutic option for the treatment of NPS associated with AD."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Zai Lab Announces Approval of COBENFY (xanomeline and trospium chloride) in China, a First-in-Class Therapy for Schizophrenia (Businesswire) - "The NMPA’s approval of COBENFY is supported by the results from a Phase 1 pharmacokinetics (PK) study conducted in China, the Phase 3 China study (ZL-2701-001), and data from three global EMERGENT clinical studies."

China approval • Schizophrenia

A Study to Evaluate Novel KarX and KarT Prototypes Versus the KarXT and KarX-EC Reference Following Single Doses, and to Explore the Effect of Food After Multiple Doses of Selected Prototypes in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Bristol-Myers Squibb | N=48 ➔ 72 | Trial completion date: Feb 2026 ➔ Aug 2026 | Trial primary completion date: Feb 2026 ➔ Aug 2026

Enrollment change • Trial completion date • Trial primary completion date

Efficacy of xanomeline and xanomeline trospium in the treatment of cognitive impairment: A systematic review of preclinical and clinical trials. (PubMed, Eur Neuropsychopharmacol) - "The convergence of preclinical and clinical findings supports the hypothesis that xanomeline trospium exerts direct pro cognitive effects in persons with schizophrenia, bipolar disorder, and potentially other neuropsychiatric conditions (e.g., AD). Limitations of the current study include limited indications investigated and the absence of a comprehensive analysis of xanomeline's overall neurobiologic effects."

Journal • Preclinical • Review • Alzheimer's Disease • Bipolar Disorder • CNS Disorders • Cognitive Disorders • Mood Disorders • Psychiatry • Schizophrenia

Efficacy and safety of xanomeline and trospium chloride for cognitive impairment in Alzheimer's disease (MINDSET-1 and MINDSET-2) (CTAD 2025) - No abstract available

Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

A Study of KarXT + KarX-EC for Treatment of Irritability in Children and Adolescents With Autism (clinicaltrials.gov) - P3 | N=176 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P3 trial • Autism Spectrum Disorder • Genetic Disorders

A Study of KarXT + KarX-EC for Treatment of Irritability in Children and Adolescents With Autism Spectrum Disorder (clinicaltrials.gov) - P3 | N=176 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P3 trial • Autism Spectrum Disorder • Genetic Disorders

A Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Schizophrenia in Adolescents (clinicaltrials.gov) - P3 | N=166 | Not yet recruiting | Sponsor: Bristol-Myers Squibb

New P3 trial • CNS Disorders • Psychiatry • Schizophrenia

Bristol Myers Squibb Announces Continuation of ADEPT-2 Phase 3 Study in Psychosis Associated with Alzheimer's Disease (Bristol-Myers Squibb Press Release) - "Following consultation and agreement with the U.S. Food and Drug Administration (FDA), an interim data analysis for efficacy and safety was conducted by an independent party and reviewed by the Data Monitoring Committee (DMC)...Following this analysis, the DMC recommended the study continue by enrolling additional patients to the original target study population. Based on this recommendation, BMS will continue patient enrollment and advance the program as advised by the DMC. BMS remains blinded to study data....Additional trial results from the ADEPT program in psychosis associated with Alzheimer's Disease, including ADEPT-2, ADEPT-1 and ADEPT-4, are expected to read out by the end of 2026."

Clinical data • DSMB • Trial status • Alzheimer's Disease • Psychiatry