FDA Approves First Schizophrenia Treatment With a Novel Target in 70 Years

The US Food and Drug Administration has granted approval to Bristol-Myers Squibb’s drug Cobenfy® (xanomeline and trospium chloride) for treating schizophrenia in adults.

Schizophrenia affects ~24 million people worldwide, according to the World Health Organization. Symptoms, including hallucinations, difficulty controlling thoughts and cognitive issues, can have serious adverse effects on an individual’s quality of life. Effective treatment options are therefore sorely needed.

Cobenfy, which is administered orally, is the first antipsychotic to target cholinergic receptors – receptors activated by the neurotransmitter acetylcholine – in schizophrenia treatment. Historically, standard of care antipsychotics for the condition have targeted dopamine receptors.

“All currently licensed antipsychotics exert effects on the dopamine system, and this has been the case for at least 50 years, said Dr. Sameer Jauhar, senior clinical lecturer in Affective Disorders and Psychosis, and consultant psychiatrist at King’s College, London and South London and Maudsley NHS Foundation Trust.

“Unfortunately currently available antipsychotics have significant side-effects, which include weight gain and movement effects, and this can affect peoples’ concordance with treatment,” Jauhar continued.

Cobenfy’s approval is based on clinical data from two five-week studies, where the drug was evaluated in a randomized, double-blind and placebo-controlled manner. Changes from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week five were measured as the primary efficacy point. Across both studies, patients receiving Cobenfy demonstrated a reduction in symptoms when compared to the placebo group.

It also appears the drug might be better tolerated by schizophrenia patients, based on available side effect data.

“The side effect profile from Phase III trials suggests it has less of the side effects noted with current treatments,” added Jauhar.

Jauhar acknowledged that the five-week duration of the clinical studies is arguably short, and longer-term trials will be necessary to inform clinical care. Nonetheless, he said, “In my opinion, as a clinician and researcher, this is possibly one of the most exciting developments in our field, and I am very excited about this.”

“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, MD, director of the Division of Psychiatry, Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “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.”

Across the pond, Dr. Robert McCutcheon, Wellcome Clinical Research Career Development Fellow in the Department of Psychiatry at the University of Oxford, told the Science Media Centre that his department will be running the first UK trial of the compound at Oxford in 2025. 

This article is a rework of a press release issued by the US Food and Drug Administration. Material has been edited for length and content.