FDA approves first new class of schizophrenia treatment in more than 30 years

Key takeaways:

• Cobenfy is the first antipsychotic medication to treat schizophrenia by targeting cholinergic receptors.
• The approval is supported by data from the EMERGENT-2 and EMERGENT-3 trials.

The FDA has approved Cobenfy, formerly known as KarXT, a muscarinic acetylcholine receptor agonist for the treatment of schizophrenia in adults.

Cobenfy (xanomeline-trospium, Bristol Myers Squibb) is the first antipsychotic medication for schizophrenia that targets cholinergic receptors rather than dopamine receptors, the FDA said. It represents the first new class of schizophrenia medication in decades.

“The approval of Cobenfy as a new class of medicine for the treatment of schizophrenia in adults is a significant step for patients and those who care for them, providing the first differentiated option in over 30 years,” Ken Kramer, PhD, vice president of Neuropsychiatry Medical Affairs at Bristol Myers Squibb, told Healio.

While Cobenfy’s exact mechanism of action is unknown, the manufacturer said in a press release that its efficacy may be related to the “agonist activity of xanomeline at M₁ and M₄ muscarinic acetylcholine receptors in the central nervous system.” Unlike currently available treatments, Cobenfy does not directly block dopamine receptors.

The approval is supported by data from the EMERGENT-2 and EMERGENT-3 trials, both of which were 5-week, randomized, double-blind, placebo-controlled, multicenter studies in adults with schizophrenia. The primary measure of efficacy was the change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 5. In both studies, Cobenfy was associated with “a meaningful reduction” in schizophrenia symptoms compared with placebo, the FDA said. Specifically, compared with placebo, Cobenfy demonstrated a 9.6-point greater reduction in PANSS in the EMERGENT-2 trial (21.2 vs. 11.6) and an 8.4-point greater reduction in the EMERGENT-3 trial (20.6 vs. 12.2), according to the manufacturer.

The prescribing information for Cobenfy includes warnings that the drug can increase heart rate, cause urinary retention and decrease gastric movement or angioedema of the face and lips, the FDA said in the release. The drug may also increase the risk for liver damage. It is not recommended for patients with mild hepatic impairment, and it “should not be used in patients with known hepatic impairment,” the FDA said.

The most common adverse events tied to Cobenfy include abdominal pain, constipation, diarrhea, dizziness, gastroesophageal reflux disease, hypertension, indigestion, nausea, tachycardia and vomiting, according to the FDA release.

“Schizophrenia is a leading cause of disability worldwide. It is a severe, chronic mental illness that is often damaging to a person’s quality of life,” Tiffany Farchione, MD, director of the FDA’s division of psychiatry, Office of Neuroscience, said in the release. “This drug takes the first new approach to schizophrenia treatment in decades. This approval offers a new alternative to the antipsychotic medications people with schizophrenia have previously been prescribed.”

Bristol Myers Squibb received rights to Cobenfy after it acquired Karuna Therapeutics. Before then, Karuna submitted a new drug application to the FDA in October 2023, and the regulatory body accepted the NDA for the novel treatment in late November 2023.

References:

• Bristol Myers Squibb completes acquisition of Karuna Therapeutics, strengthening neuroscience portfolio. https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-Completes-Acquisition-of-Karuna-Therapeutics-Strengthening-Neuroscience-Portfolio/default.aspx. Published March 18. 2024. Accessed Sept. 27, 2024.
• FDA approves drug with new mechanism of action for treatment of schizophrenia. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia. Published Sept. 26, 2024. Accessed Sept. 27, 2024.
• U.S. Food and Drug Administration approves Bristol Myers Squibb’s Cobenfy (xanomeline and trospium chloride), a first-in-class muscarinic agonist for the treatment of schizophrenia in adults. https://www.businesswire.com/news/home/20240925382351/en/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibb%E2%80%99s-COBENFY%E2%84%A2-xanomeline-and-trospium-chloride-a-First-In-Class-Muscarinic-Agonist-for-the-Treatment-of-Schizophrenia-in-Adults. Published Sept. 26, 2024. Accessed Sept. 27, 2024.