The FDA has approved Cobenfy (xanomeline and trospium chloride), marking the first new medication for schizophrenia in decades. The therapy selectively targets M1 and M4 receptors in the brain, distinguishing it from current antipsychotic therapies that primarily block dopamine receptors.

Cobenfy’s approval is supported by data from the EMERGENT trial, which included three placebo-controlled efficacy trials and two long-term open-label trials. In the phase 3 EMERGENT-2 and EMERGENT-3 trials, Cobenfy demonstrated statistically significant reductions in schizophrenia symptoms, as measured by the Positive and Negative Syndrome Scale (PANSS). In EMERGENT-2, Cobenfy reduced symptoms by 9.6 points (-21.2 Cobenfy vs. -11.6 placebo, p < 0.0001) from baseline at week 5, while EMERGENT-3 showed an 8.4-point reduction (-20.6 Cobenfy vs. -12.2 placebo, p < 0.0001).

The drug was generally well-tolerated across both acute and long-term trials. Common adverse reactions (≥ 5%) included nausea, constipation, vomiting, hypertension, and dyspepsia. Cobenfy is contraindicated in patients with urinary retention, moderate or severe hepatic impairment, gastric retention, or a history of hypersensitivity to trospium chloride.

Clinicians should monitor patients for urinary retention, liver function abnormalities, and increases in heart rate during treatment. The safety and tolerability profile of Cobenfy was established in trials with up to 1 year of follow-up, with no atypical antipsychotic class warnings or boxed warnings associated with the drug.