▎WuXiEdited by Kant Content Team

Recently, Bristol Myers Squibb Company announced the latest interim data from its Phase 3 clinical trial EMERGENT-4 for the potential "first-in-class" therapy KarXT (xanomeline-trospium) used to treat adult patients with schizophrenia. The results showed,After 52 weeks of KarXT treatment, symptoms of schizophrenia significantly improved across all efficacy measures.PreviouslyThe New Drug Application (NDA) for KarXT for the treatment of adult schizophrenia has been submitted to the U.S. FDA.Acceptance, with a PDUFA target date of September 26, 2024.According to the press release, if approved, KarXT will become the first new mechanism drug for treating schizophrenia in decades.

EMERGENT-4 is a 52-week Phase 3 open-label extension study designed to evaluate the long-term safety, tolerability, and efficacy of KarXT in adult patients with schizophrenia who have previously completedA 5-week, double-blind, placebo-controlled Phase 3 trial for efficacy and safetyEMERGENT-2 orOne of the items in EMERGENT-3。As of the data as of April 17, 2023, a total of 110 patients participated in the interim efficacy analysis, of which 29 patients had completed 52 weeks of treatment.

The interim analysis showed that at 52 weeks, KarXT significantly improved efficacy outcomes for all symptoms in patients with schizophrenia. According to the Positive and Negative Syndrome Scale (PANSS) scores, at the end of the open-label extension period,More than 75% of patients experienced over 30% improvement in symptoms, with an average reduction of 33.3 points compared to baseline (98.4 points).In addition,The subjects' Clinical Global Impression-Severity (CGI-S) scores improved by an average of 1.7 points compared to baseline (5.2 points).From "significant discomfort" at baseline to "moderate discomfort" or "mild discomfort" one year later.

During the 52-week trial, improvements in schizophrenia symptoms persisted regardless of whether participants had previously received KarXT or placebo treatment during the acute trial period.Before participating in the open-label extension trial, patients who had received placebo treatment in the EMERGENT-2 and EMERGENT-3 trials had significantly higher mean PANSS scores than those treated with KarXT (86.5 vs. 76.1). Patients previously on placebo showed marked symptom improvement within two weeks of starting KarXT treatment. After four weeks, PANSS scores were comparable between patients treated with KarXT or placebo in the acute trial.

In addition,KarXT also had a positive impact on patients' weight and long-term metabolic status.Most patients showed stabilization or improvement in metabolic parameters over the 52-week treatment period. In long-term trials, KarXT was generally well-tolerated, with side effects consistent with previous KarXT trials conducted on patients with schizophrenia. Over the 52-week treatment period, KarXT did not cause significant changes in prolactin levels or clinically meaningful changes in movement disorder scale scores.

KarXT is a product developed by Karuna Therapeutics.Oral M1/M4 Muscarinic Acetylcholine Receptor Agonist, is being developed for the treatment of mental and neurological disorders, including schizophrenia and dementia-related psychotic disorders,Has the potential to become the first non-targeted dopaminergic and serotonergic signaling pathway drug with a dual mechanism.In December 2023, Bristol-Myers Squibb reached a total amount of approximately $14 billionAcquisitionAcquired Karuna and obtained KarXT. Zai Lab has the development rights for this innovative therapy in Greater China.KarXTIn 2022, it has already been in ChinaApproved for Clinical Use。

KarXT consists of two active ingredients, xanomeline and trospium chloride, designed to activate muscarinic acetylcholine receptors in the brain while minimizing effects on peripheral muscarinic acetylcholine receptors.By stimulating muscarinic receptors M1 and M4, xanomeline can alleviate negative symptoms such as apathy, reduced social drive, improve cognitive abilities, and is highly beneficial for improving other psychiatric symptoms like hallucinations and delusions. The quaternary ammonium compound trospium chloride, a muscarinic receptor antagonist, can inhibit the peripheral side effects of xanomeline.

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