The first new schizophrenia drug in more than 30 years cleared the U.S. Food and Drug Administration on Thursday, Sept. 26, 2024. Cobenfy, from Bristol Myers Squibb, pairs xanomeline with trospium chloride and is taken as a twice-daily pill.
In clinical trials, the combination helped control hallucinations, delusions and disorganized thinking.
“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,” said Tiffany Farchione, M.D., director of the Division of Psychiatry in the FDA’s Office of Neuroscience. “This drug takes the first new approach to schizophrenia treatment in decades.”
A different target
The first schizophrenia drugs, chlorpromazine and haloperidol (sold as Thorazine and Haldol), arrived in the 1950s. Few new medications followed, and most later approvals were variations on those older drugs.
Most antipsychotics change levels of dopamine, a brain chemical tied to mood, motivation and thinking, psychiatrist Jelena Kunovac, MD, explained to ABC News. Cobenfy adjusts acetylcholine, which aids memory, learning and attention. “We are overdue for a medication that targets schizophrenia with a different mechanism of action,” she said.
Yale Medicine’s Vinod Srihari, MD, noted that Cobenfy targets muscarinic receptors, which may affect dopamine indirectly. Researchers have not pinned down its exact mechanism. Xanomeline was tested in the late 1990s for cognitive decline in Alzheimer’s disease, and it showed unexpected benefits for psychotic symptoms. Nausea, vomiting and other gut problems stalled that work. Trospium chloride was added to reduce them.
Side effects and the trial record
Clinical trials suggest the drug may ease symptoms without the weight gain, drowsiness and movement disorders common with older drugs. Those effects can grow so unpleasant that, in some studies, many patients quit within 18 months. Samit Hirawat, the company’s chief medical officer, said only 6% of patients stopped Cobenfy over side effects, against “the 20-30% seen with older antipsychotic drugs.”
Cobenfy has its own side effects, according to the FDA. The most common are nausea, indigestion, constipation, vomiting, hypertension, abdominal pain, diarrhea, increased heart rate, dizziness and gastroesophageal reflux disease. The company also reports a risk of liver damage. There is no FDA boxed warning.
Approval rested on two identically designed studies with 252 participants in total. Both were five-week, randomized, double-blind, placebo-controlled trials in adults with schizophrenia. In November 2024, the company presented data from two 52-week extension trials that, it says, pointed to continued safety and symptom improvement.
Srihari urged some patience. A boxed warning’s absence is “not a real accomplishment” for a drug tested on relatively few people over five weeks, he said. A new drug only has to beat placebo to reach the U.S. market, he added, so comparisons with existing medications and rare or long-term side effects wait for post-marketing studies. He called that “a limitation of the current FDA approval process,” not a criticism of the trials. Whether Cobenfy helps with withdrawal, low motivation or problems with working memory is still unknown.
Who may benefit
“It may prove advantageous to those who don’t tolerate what has been available,” said Dr. Leslie Citrome of New York Medical College. He thinks people who struggle with the side effects of traditional drugs may gain the most, and that a different mechanism offers hope to those who have not responded to existing treatments.
Schizophrenia affects about 24 million people worldwide, or roughly one in 300, according to the World Health Organization. It usually begins in late adolescence or early adulthood. About 1% of Americans, roughly 3 million people, live with it.
Adam Lenkowsky, the company’s chief commercialization officer, said doctors could begin prescribing Cobenfy by the end of October. Studies of the drug for Alzheimer’s disease and bipolar disorder are underway.
Srihari advises anyone considering the drug to talk openly with their prescriber and ask their insurer about coverage. Medication is one piece of care, he added, alongside psychotherapy, family education and support for work or school goals.
Sources
- FDA approves 1st new drug to treat schizophrenia in more than 30 years
- 3 Things to Know About Cobenfy, the New Schizophrenia Drug
- FDA approves 1st new drug for schizophrenia in more than 30 years
