KarXT (xanomeline-trospium) was found to significantly reduce symptoms of schizophrenia in adult patients, according to topline results from the phase 3 EMERGENT-3 trial.
KarXT is an oral, investigational therapy that combines xanomeline, a muscarinic agonist, and trospium chloride, a muscarinic antagonist. The treatment is designed to stimulate muscarinic receptors in the central nervous system without relying on the dopaminergic or serotonergic pathway.
The EMERGENT-3 trial (ClinicalTrials.gov Identifier: NCT04738123) included 256 patients with schizophrenia who were experiencing symptoms of psychosis. Patients were randomly assigned 1:1 to receive either KarXT or placebo twice daily for 5 weeks. The primary endpoint was the change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at week 5.
Findings showed that treatment with KarXT resulted in a statistically significant and clinically meaningful 8.4-point reduction in PANSS total score at week 5 compared with placebo (-20.6 for KarXT vs -12.2 for placebo; P <.0001). Significant symptom reduction was observed as early as week 2 (P <.05) in the KarXT group and maintained across all timepoints. KarXT was also associated with a statistically significant 3.5-point reduction in PANSS positive subscale compared with placebo at week 5 (-7.1 for KarXT vs -3.6 for placebo; P <.0001).
The safety profile of KarXT was consistent with that observed in previous trials. The most common treatment emergent adverse events were nausea, dyspepsia, vomiting, constipation, headache, hypertension, diarrhea, and insomnia, which were all rated mild or moderate in severity.
“KarXT has now demonstrated a robust and consistent reduction of symptoms across all 3 registrational trials, providing a compelling picture of the potential of KarXT in schizophrenia,” said Bill Meury, president and CEO of Karuna Therapeutics. “With these data, we are one step closer to a potential treatment option that could provide the first new mechanism of action to treat schizophrenia in several decades.”
The Company expects to submit a New Drug Application to the Food and Drug Administration in mid-2023. The application is also supported by previously reported data from the EMERGENT-2 trial (ClinicalTrials.gov Identifier: NCT04659161), along with the EMERGENT-1 (ClinicalTrials.gov Identifier: NCT03697252), EMERGENT-4 (ClinicalTrials.gov Identifier: NCT04659174), and EMERGENT-5 (ClinicalTrials.gov Identifier: NCT04820309) trials.
Karuna Therapeutics announces positive results from phase 3 EMERGENT-3 trial of KarXT in schizophrenia. News release. Karuna Therapeutics. Accessed March 20, 2023. https://www.businesswire.com/news/home/20230320005250/en/Karuna-Therapeutics-Announces-Positive-Results-from-Phase-3-EMERGENT-3-Trial-of-KarXT-in-Schizophrenia.