FDA Approves Cobenfy for Schizophrenia in Adults

On Thursday, November 14, 2024, the U.S. Food and Drug Administration (FDA) announced the approval of Cobenfy, a medication combining xanomeline and trospium chloride, for the treatment of schizophrenia in adults. This novel treatment represents the first new class of medicine for schizophrenia in decades. Cobenfy is a muscarinic agonist that selectively interacts with M1 and M4 receptors in the brain without affecting D2 receptors, marking a significant advancement in the approach to treating this mental health condition.

The approval of Cobenfy is founded on the results of the EMERGENT clinical trials. These included the phase 3 EMERGENT-2 and EMERGENT-3 trials, where Cobenfy successfully met its primary endpoint. The trials demonstrated that Cobenfy significantly reduced schizophrenia symptoms compared to a placebo, with the EMERGENT-2 trial showing a 9.6-point reduction and the EMERGENT-3 trial showing an 8.4-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 5. Additionally, in the EMERGENT-2 trial, Cobenfy achieved a significant improvement in the Clinical Global Impression-Severity (CGI-S) score, a secondary endpoint, by week 5.

Throughout both clinical trials, the most commonly reported adverse reactions to Cobenfy, occurring in at least 5 percent of patients and at a rate twice that of the placebo, included nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness, and gastroesophageal reflux disease.

Dr. Rishi Kakar, an investigator involved in the EMERGENT trials, highlighted the variability and complexity of schizophrenia, emphasizing that it often necessitates switching and discontinuing therapies. He noted that Cobenfy, by engaging a novel pathway, presents a valuable new option for managing this challenging condition.

The approval of Cobenfy was granted to Bristol Myers Squibb.