Zai Lab announced positive topline results from its Phase 3 multi-center trial evaluating KarXT (xanomeline and trospium chloride) for the treatment of schizophrenia in China. The registrational bridging trial met its primary endpoint, demonstrating a statistically significant reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared to placebo at Week 5.
The study, which involved 202 acutely psychotic hospitalized adult patients with schizophrenia, showed a 9.2-point reduction in PANSS total score with KarXT compared to placebo (-16.9 vs. -7.7, p=0.0014). This indicates a clinically meaningful improvement in overall schizophrenia symptoms.
Secondary Endpoint Achievements
The trial also met all key secondary efficacy endpoints. These included:
- A 1.9-point reduction in the PANSS positive symptom subscale with KarXT compared to placebo (-6.5 vs. -4.6, p=0.0474).
- A 2.5-point reduction in the PANSS negative subscale with KarXT compared to placebo (-3.2 vs. -0.7, p=0.0062).
- Significant improvement in PANSS negative Marder factor score and Clinical Global Impression-Severity (CGI-S) scale at week five compared to placebo.
These results collectively suggest that KarXT can address both the positive and negative symptoms of schizophrenia, offering a more comprehensive treatment approach.
Safety and Tolerability
The safety profile of KarXT in this trial was consistent with previous global studies. 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. No new or unexpected safety signals were observed.
Regulatory Pathway and Clinical Significance
Based on these positive results, Zai Lab is moving forward with plans to submit a New Drug Application (NDA) to China’s National Medical Products Administration (NMPA) in early 2025. If approved, KarXT could offer a new treatment option for the over 8 million people in China living with schizophrenia.
"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 that fewer than half of those with schizophrenia in China receive treatment, and many more do not get adequate symptom relief from available antipsychotics.
KarXT Mechanism of Action
KarXT (xanomeline and trospium chloride) is an oral M1/M4-preferring muscarinic acetylcholine receptor agonist in combination with a muscarinic acetylcholine receptor antagonist. Xanomeline preferentially stimulates muscarinic receptors in the central nervous system, offering a different mechanism of action compared to current antipsychotics that primarily target dopamine or serotonin receptors.
Schizophrenia in China
Schizophrenia affects nearly 24 million people worldwide, with over 8 million in China. Many patients experience limited efficacy or problematic side effects from current antipsychotic therapies, highlighting the need for more effective and tolerable treatments.
