Zai Lab Limited announced positive topline results from its Phase 3 multi-center trial evaluating the safety and efficacy of KarXT (xanomeline and trospium chloride) in treating schizophrenia in China. The registrational bridging trial met its primary endpoint, showing a statistically significant 9.2-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo at Week 5 (-16.9 KarXT vs. -7.7 placebo, p=0.0014). These findings suggest KarXT could offer a novel treatment option for the over 8 million people in China living with schizophrenia.
The study (ZL-2701-001) also met all key secondary efficacy endpoints, demonstrating a significant improvement in PANSS positive symptom subscale score (p=0.0474), PANSS negative symptom subscale score (p=0.0062), PANSS negative Marder factor score, the Clinical Global Impression-Severity (CGI-S) scale at week five and percentage of PANSS responders at week five compared to placebo. Key secondary endpoints were formally tested sequentially in a predefined order.
Safety Profile
The trial revealed no new or unexpected safety signals compared to prior KarXT trials in schizophrenia. Treatment emergent adverse events in the treatment arm that occurred at ≥ 10% and at least twice the rate in placebo include vomiting, tachycardia, nausea, systemic hypertension, dizziness and diarrhea.
Regulatory Plans
Based on these results, Zai Lab intends to submit a new drug application (NDA) to China’s National Medical Products Administration (NMPA) for KarXT in schizophrenia in early 2025.
Expert Commentary
"The positive findings we observed in this bridging trial will contribute to a large global dataset for KarXT and demonstrate that this novel compound has the potential to be an important new treatment option for adults with schizophrenia in China," said Rafael G. Amado, M.D., President, Head of Global Research and Development, Zai Lab. "More than 8 million people in China live with schizophrenia, and fewer than half receive treatment, while many more do not get adequate symptom relief and suffer debilitating side effects from available antipsychotic therapies."
Gang Wang, M.D., Director of National Clinical Research Center for Mental Disorders, Dean of Beijing Anding Hospital, Capital Medical University and the leading principal investigator in the Zai Lab Phase 3 trial, added, "We see on a daily basis the need for more effective and tolerable treatment options for patients living with schizophrenia in Greater China. We are encouraged that the data from this study further support KarXT as an impactful treatment option for these patients."
Trial Design
The Zai Lab Phase 3 trial was a multi-center, randomized, placebo-controlled study that evaluated the efficacy and safety of KarXT in 202 acutely psychotic hospitalized adult patients with schizophrenia in China. The study comprised two parts: a five-week double-blind part followed by a 12-week open-label extension part. The results shared pertain to the five-week, double-blind trial segment.
About KarXT
KarXT (xanomeline and trospium chloride) is an oral M1/M4-preferring muscarinic acetylcholine receptor agonist in combination with a muscarinic acetylcholine receptor antagonist. It is under development for psychiatric conditions, including schizophrenia and Alzheimer’s-related psychosis. Xanomeline preferentially stimulates muscarinic receptors in the central nervous system implicated in these conditions, unlike current antipsychotics that primarily target dopamine or serotonin receptors. Zai Lab holds an exclusive license from Bristol Myers Squibb (following its acquisition of Karuna Therapeutics) to develop, manufacture, and commercialize KarXT in Greater China.
Schizophrenia in China
More than 8 million people in China are living with schizophrenia, yet fewer than half are receiving treatment, and even fewer are obtaining adequate symptom improvement using current antipsychotics. There is a significant need for more effective therapies with improved safety to treat serious psychiatric conditions for patients with schizophrenia in Greater China.
