On December 23, Zai Lab announced that the NMPA (National Medical Products Administration) has approved its New Drug Application (NDA) for xenometrine trastuzumab capsules for the treatment of schizophrenia in adults . The press release stated that this is the first approved schizophrenia therapy with a novel mechanism of action in over 70 years, representing a fundamental breakthrough in the treatment of schizophrenia.KarXT is an oral combination of an M1/M4 type muscarinic acetylcholine receptor agonist and a muscarinic receptor antagonist. Unlike traditional dopamine-targeting antipsychotics, KarXT affects core disease pathways by selectively acting on muscarinic acetylcholinesteric M1 and M4 receptors in the brain.In November 2021, Zai Lab acquired the development and commercialization rights for KarXT in Greater China (including mainland China, Hong Kong, Macau, and Taiwan) from Karuna Therapeutics for $187 million . In December 2023, BMS acquired Karuna for $14 billion , adding the product to its pipeline.In September 2024, the U.S. FDA approved the drug for the treatment of schizophrenia in adults. The approval was primarily based on efficacy and long-term safety data from the EMERGENT studies. In the global Phase III EMERGENT-2 and EMERGENT-3 studies, KarXT met its primary endpoint, demonstrating a statistically significant reduction in schizophrenia symptoms compared to placebo .
In terms of sales data, KarXT earned $10 million in just three months after its launch in 2024 , and its sales jumped to $62 million in the first half of 2025. Evaluate listed it as one of the top ten potential blockbuster drugs in its 2024 report and predicted that the drug's sales could reach $3.1 billion by 2030 .
The NMPA's approval of KarXT is based on data from a Phase I pharmacokinetic study conducted in China, a Phase III clinical trial in China (ZL-2701-001), and three global EMERGENT clinical trials.
In October 2024, Zai Lab announced primary data from its Phase III multicenter clinical trial in China evaluating the safety and efficacy of KarXT. Consistent with previous global clinical studies, this registrational study met its primary endpoint, demonstrating a statistically significant reduction in the PANSS total score of KarXT at week 5 compared to placebo (-16.9 KarXT vs. -7.7 placebo, p=0.0014) .
The study also met all key secondary efficacy endpoints. At week five, compared with placebo, there were significant improvements in PANSS positive symptom subscale scores, PANSS negative symptom subscale scores, PANSS Marder negative symptom factor scores, Clinical Global Impression Severity (CGI-S) scores, and the percentage of PANSS respondents at week five . Key secondary endpoints were formally tested in a pre-specified order.
The findings at week 5 included:
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On the PANSS positive symptom subscale, KarXT decreased by 1.9 points compared to placebo (-6.5 KarXT vs. -4.6 placebo, p=0.0474) .
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On the PANSS negative symptom subscale, KarXT decreased by 2.5 points compared to placebo (-3.2 KarXT vs. -0.7 placebo, p=0.0062) .
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Compared to previous studies of KarXT in schizophrenia, no new or unexpected safety signals were observed in this study. Treatment-related adverse events occurring in ≥10% of the treatment group and at least twice as frequently as in the placebo group included vomiting, tachycardia, nausea, systemic hypertension, dizziness, and diarrhea.
It is worth mentioning that in September of this year, the Chinese Medical Association's "Guidelines for the Prevention and Treatment of Schizophrenia in China (2025 Edition)" included KarXT as an innovative therapy, marking the first time this drug has been included in a national-level guideline.
In the field of schizophrenia, new drugs with relatively rapid development progress include Merck's PDE10A inhibitor MK-8189 and Sorrento's mGlu2/3 receptor agonist DB103 , which have entered Phase II clinical trials .
It is worth noting that since 2024, several drugs in this field have failed in their marketing campaigns, including AbbVie's Emraclidine (which failed Phase II in November 2024), Iclepertin (which failed Phase III in January 2025), and Luvadaxistat (which failed Phase II in September 2024).
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