On December 23, Zai Lab officially announced that the National Medical Products Administration (NMPA) of China has approved the New Drug Application (NDA) for Xanomeline-Trospium Chloride Capsules (Brand name: KarXT®/Kaigele®), indicated for the treatment of adult patients with schizophrenia. The press release noted that this marks the first approved schizophrenia therapy with a novel mechanism of action in more than 70 years. Unlike traditional antipsychotics that target dopamine receptors, KarXT® exerts its effects on core disease pathways by selectively acting on muscarinic acetylcholine M1 and M4 receptors in the brain.

Schizophrenia affects over 8 million adults in China, yet fewer than half of them receive formal treatment. The disease severely impairs patients’ abilities to think, feel, and behave, characterized by positive symptoms, negative symptoms, and cognitive impairments. Unfortunately, many patients continue to face inadequate symptom relief or adverse effects during treatment with existing antipsychotic medications.

Statistics show that approximately 75% of schizophrenia patients discontinue their medication within 18 months of starting treatment. Treatment discontinuation often leads to serious consequences such as disease relapse, hospitalization, and prolonged remission periods. Globally, schizophrenia affects nearly 24 million people, with antipsychotic medications being the most commonly used treatment. Compared with the general population, individuals with schizophrenia have a reduced life expectancy by 10 to 20 years.

KarXT® (Xanomeline-Trospium Chloride Capsules) is an oral combination of a muscarinic acetylcholine M1/M4 receptor agonist and a muscarinic receptor antagonist. Its mechanism of action is completely distinct from that of traditional antipsychotics, which primarily target dopamine or serotonin receptors. This novel mechanism is regarded as a fundamental breakthrough in schizophrenia treatment since the introduction of chlorpromazine in the 1950s, ending a 70-plus-year era without new mechanism-based drugs in this field.

Specifically, xanomeline, one component of the drug, can cross the blood-brain barrier to stimulate disease-related M1 and M4 receptors in the central nervous system; trospium chloride, the other component, poorly penetrates the blood-brain barrier and mainly acts peripherally, designed to mitigate adverse reactions caused by peripheral cholinergic activation.

The NMPA approval is supported by data from a Phase I pharmacokinetic study, a Phase III clinical trial conducted in China, as well as three global EMERGENT clinical studies.

Among these, the Phase III multicenter clinical trial in China achieved its primary endpoint. Results showed that at Week 5, KarXT® reduced the total score of the Positive and Negative Syndrome Scale (PANSS) by 9.2 points compared with placebo, representing a statistically significant improvement.

The trial also met all key secondary efficacy endpoints. Specific data included a 1.9-point reduction in the PANSS Positive Symptom Subscale and a 2.5-point reduction in the PANSS Negative Symptom Subscale versus placebo. These results were consistent with those of the global clinical studies. Data from the global Phase III EMERGENT-2 study demonstrated that patients in the KarXT® group achieved a statistically significant reduction in the total PANSS score from baseline compared with the placebo group.

In the Phase III clinical trial conducted in China, the safety profile of KarXT® was consistent with that of the global studies, with no new or unexpected safety signals identified. Treatment-related adverse events (TRAEs) that occurred at a higher incidence in the treatment group and were at least twice as frequent as in the placebo group included vomiting, tachycardia, nausea, systemic hypertension, dizziness, and diarrhea. These adverse reactions were mainly concentrated in the gastrointestinal and cardiovascular systems.

Global study data provided further details. In the EMERGENT-2 study, the most common adverse events in the KarXT® group included constipation (21%), nausea (19%), and vomiting (14%). The study also showed that the incidence rates of extrapyramidal motor symptoms and akathisia in the KarXT® group were similar to those in the placebo group, both ranging from 0% to 1%.

The commercial prospects of KarXT® are widely optimistic in the industry, and preliminary sales data have proven its market acceptance. In 2024, the drug generated USD 10 million in sales just three months after its launch in the United States; its sales soared to USD 62 million in the first half of 2025.

Zai Lab has long prepared its commercial layout for the drug. In November 2021, Zai Lab in-licensed the development and commercialization rights to KarXT® in Greater China from Karuna Therapeutics for USD 187 million. In December 2023, Bristol Myers Squibb (BMS) acquired Karuna Therapeutics for USD 14 billion, integrating the product into its pipeline to further accelerate its global commercialization process.