Zai Lab announced that the China National Medical Products Administration (NMPA) has accepted the New Drug Application (NDA) for KarXT (xanomeline and trospium chloride) for the treatment of schizophrenia in adults. This marks a significant step toward potentially redefining the treatment landscape for the over 8 million individuals in China living with schizophrenia.
The NDA is supported by data from a Phase 1 China Pharmacokinetics (PK) study, the Phase 3 China study (ZL-2701-001), and the global EMERGENT clinical programs. KarXT demonstrated statistically significant improvements in schizophrenia symptoms and a tolerable safety profile in these trials.
Clinical Trial Results
The Phase 3 China study met its primary endpoint, demonstrating a statistically significant 9.2-point difference from placebo in the reduction in the Positive and Negative Syndrome Scale (PANSS) total score from baseline at Week 5 (-16.9 KarXT vs. -7.7 placebo, p=0.0014). Key secondary efficacy endpoints also showed significant improvement, including PANSS positive and negative symptom subscales, the Clinical Global Impression-Severity (CGI-S) scale, and the percentage of PANSS responders at week five compared to placebo.
According to Gang Wang, M.D., Dean of Beijing Anding Hospital, Capital Medical University and the leading principal investigator for the Phase 3 China study, "KarXT is the first new class of treatment for patients with schizophrenia in several decades. We are excited about this potentially transformative treatment option in clinical settings to benefit these patients as early as possible."
Safety and Tolerability
The safety profile of KarXT in the China study was consistent with prior trials, with no new or unexpected safety signals. Common treatment-emergent adverse events included vomiting, tachycardia, nausea, systemic hypertension, dizziness, and diarrhea.
Mechanism of Action
KarXT is a combination of xanomeline, an oral M1/M4-preferring muscarinic acetylcholine receptor agonist, and trospium chloride, a muscarinic acetylcholine receptor antagonist. Xanomeline stimulates muscarinic receptors in the central nervous system, offering a different mechanism compared to current antipsychotics that primarily target dopamine or serotonin receptors.
Schizophrenia Treatment Landscape
Schizophrenia is a chronic and debilitating mental illness characterized by positive symptoms (hallucinations, delusions), negative symptoms (social withdrawal, lack of emotion), and cognitive impairment. Current treatments often have limited efficacy and undesirable side effects, leading to high rates of medication discontinuation. It is estimated that more than 8 million people in China are living with schizophrenia, and there is a significant need for more effective and safer therapies.
Dr. Rafael Amado, M.D., President, Head of Global Research and Development at Zai Lab, stated, "There are more than 8 million patients living with schizophrenia in China who face significant unmet needs due to the limited efficacy and undesirable side effects of current treatment options. In clinical trials, KarXT demonstrated statistically significant reductions of schizophrenia symptoms along with a tolerable safety profile. If approved, KarXT has the potential to redefine the treatment landscape."
