Positive topline results were announced from a phase 3 trial evaluating the efficacy and safety of KarXT (xanomeline-trospium) for the treatment of adults with schizophrenia.
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 multicenter, randomized, double-blind, placebo-controlled EMERGENT-2 trial (ClinicalTrials.gov Identifier: NCT04659161) included 252 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.
Treatment with KarXT resulted in a statistically significant and clinically meaningful 21.2-point reduction in the PANSS total score at week 5 compared with an 11.6-point reduction with placebo (treatment difference: 9.6; P <.0001). Significant symptom reduction was observed as early as week 2 in the KarXT group and maintained across all timepoints.
KarXT was also associated with statistically significant reductions vs placebo in key secondary endpoints: PANSS positive subscale (-6.8 vs -3.9; P <.0001); PANSS negative subscale (-3.4 vs -1.6; P =.0055); and PANSS negative Marder factor subscale (-4.2 vs -2.0; P =.0022).
The most common adverse events reported with KarXT included constipation, dyspepsia, nausea, vomiting, headache, increases in blood pressure, dizziness, gastroesophageal reflux disease, abdominal discomfort, and diarrhea.
“These data build on the growing body of clinical evidence supporting the potential of KarXT as a new and differentiated approach for schizophrenia, demonstrating notable improvements across both positive and negative symptoms, while not being associated with common problematic side effects of current therapies, such as weight gain, sedation and movement disorders,” said Rishi Kakar, MD, CSO, Segal Trials and lead investigator of the phase 3 EMERGENT-2 trial. “This unique profile of KarXT has the potential to provide a new meaningful treatment option for our patients and their families beyond the current standard of care.”
The EMERGENT program also includes 3 additional phase 3 trials (EMERGENT-3 [ClinicalTrials.gov Identifier: NCT04738123], EMERGENT-4 [ClinicalTrials.gov Identifier: NCT04659174], and EMERGENT-5 [ClinicalTrials.gov Identifier: NCT04820309]), along with the phase 2 EMERGENT-1 trial (ClinicalTrials.gov Identifier: NCT03697252).
The Company plans to submit a New Drug Application with the Food and Drug Administration in mid-2023.
Karuna Therapeutics announces positive results from phase 3 EMERGENT-2 trial of KarXT in schizophrenia. News release. Karuna Therapeutics, Inc. Accessed August 8, 2022. https://www.businesswire.com/news/home/20220808005222/en/Karuna-Therapeutics-Announces-Positive-Results-from-Phase-3-EMERGENT-2-Trial-of-KarXT-in-Schizophrenia