FDA Approves the First New Type of Schizophrenia Drug in Decades

• The FDA has approved Cobenfy, the first new type of schizophrenia drug in decades.
• Cobenfy doesn’t appear to have the same severe side effects as older antipsychotic medicines — like weight gain, involuntary muscle movement, and sedation — that can lead patients to discontinue treatment.
• Common side effects in trials included constipation, indigestion, nausea, vomiting, headaches, high blood pressure, and dizziness.

The U.S. Food and Drug Administration (FDA) has approved Cobenfy (xanomeline and trospium chloride) to treat schizophrenia in adults, offering the first new treatment in decades for the psychiatric disorder.

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“This approval offers a new alternative to the antipsychotic medications people with schizophrenia have previously been prescribed,” Tiffany Farchione, MD, director of the division of psychiatry in the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, said in the FDA statement.

Cobenfy, previously called KarXT, is the first drug in a new family of medicines known as muscarinic agonists that work by activating two receptors in the brain. Unlike previous antipsychotics, which target dopamine receptors in the brain, Cobenfy homes in on cholinergic receptors, the FDA said in its statement.

“Importantly, because KarXT acts by a fundamentally different mechanism, it does not induce the severe side effects that are observed with previous schizophrenia medications,” says P. Jeffrey Conn, PhD, a professor emeritus and founding director of the Warren Center for Neuroscience Drug Discovery at Vanderbilt University School of Medicine in Nashville, Tennessee.

“KarXT does not induce excessive weight gain, metabolic syndrome, motor disturbances [involuntary tremors], sedation, and other side effects that are commonly seen with previous medicines,” Dr. Conn says. “Avoiding these side effects is a major advantage of KarXT.”

Cobenfy Is Safe and Effective for Schizophrenia

Two late-stage clinical trials found Cobenfy safe and effective for adults with schizophrenia who were experiencing an acute psychotic episode. Both trials randomly assigned about 250 patients to take either Cobenfy or a placebo for five weeks. Researchers then used a rating system known as the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) to see how much treatment improved patient symptoms. Lower PANSS scores indicate reduced symptom severity.

By the end of treatment in the first trial, Cobenfy reduced PANSS scores by 20.6 points, significantly more than the 12.2 point reduction seen with a placebo, according to findings published in JAMA Psychiatry.

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Similarly, Cobenfy reduced PANSS scores by 21.2 points after a five-week treatment course in the second trial, significantly more than the 11.6 point reduction seen with a placebo, according to findings published in The Lancet.

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The most common side effects in the two trials were constipation, indigestion, nausea, vomiting, headaches, high blood pressure, and dizziness.

Who Should Take Cobenfy?

Some patients who don’t get enough symptom relief from older antipsychotics, or who experience side effects like sexual dysfunction, excessive weight gain, serious sleep problems, or involuntary tremors, may want to consider switching to Cobenfy, says Christoph Correll, MD, a professor of psychiatry and molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra-Northwell in Hempstead, New York.

“KarXT could potentially be a new treatment option for those patients with schizophrenia who do not respond well to currently available antipsychotics due to lack of efficacy and/or significant side effects,” says Xiaoduo Fan, MD, MPH, a psychiatry professor at UMass Chan Medical School in Worcester, Massachusetts.