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) for the treatment of schizophrenia in China. The registrational bridging trial, consistent with previous global studies, met its primary endpoint. The results indicate that KarXT could become an important new treatment option for adults with schizophrenia in China, where over 8 million people are affected by the condition.
The Phase 3 trial (ZL-2701-001) was a randomized, placebo-controlled study involving 202 acutely psychotic hospitalized adult patients with schizophrenia in China. The trial consisted of a five-week double-blind phase followed by a 12-week open-label extension. The reported results pertain to the initial five-week, double-blind segment.
Efficacy Results
KarXT demonstrated a statistically significant 9.2-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score from baseline at Week 5 compared to placebo (-16.9 KarXT vs. -7.7 placebo, p=0.0014). The trial also met all key secondary efficacy endpoints, demonstrating significant improvements in:
- PANSS positive symptom subscale score: 1.9-point reduction with KarXT compared to placebo (-6.5 KarXT vs. -4.6 placebo, p=0.0474).
- PANSS negative symptom subscale score: 2.5-point reduction with KarXT compared to placebo (-3.2 KarXT vs. -0.7 placebo, p=0.0062).
- PANSS negative Marder factor score
- Clinical Global Impression-Severity (CGI-S) scale at week five
- Percentage of PANSS responders at week five
Safety Profile
The safety profile of KarXT in this trial was consistent with prior studies, with no new or unexpected safety signals identified. Treatment-emergent adverse events occurring in the treatment arm at ≥ 10% and at least twice the rate in placebo included vomiting, tachycardia, nausea, systemic hypertension, dizziness, and diarrhea.
Regulatory Plans and Expert Commentary
Based on these results, Zai Lab is planning to submit a New Drug Application (NDA) to China’s National Medical Products Administration (NMPA) for KarXT in schizophrenia in early 2025.
"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. He also noted the significant unmet need in China, where many patients do not receive treatment or adequate symptom relief from existing 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, stated, "We are encouraged that the data from this study further support KarXT as an impactful treatment option for these patients."
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 being developed for psychiatric conditions, including schizophrenia and Alzheimer’s-related psychosis. Zai Lab holds an exclusive license from Karuna Therapeutics (now a Bristol Myers Squibb company) to develop, manufacture, and commercialize KarXT in Greater China.
