The US Food and Drug Administration (FDA) has approved Cobenfy (xanomeline and trospium chloride) capsules for the treatment of schizophrenia in adults.

It is the first antipsychotic drug approved to treat schizophrenia that targets cholinergic receptors as opposed to dopamine receptors, which has long been the standard of care.

“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, 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.”

Cobenfy’s effectiveness for the treatment of schizophrenia in adults was evaluated in two studies. Study 1 and Study 2 were five-week, randomised, double-blind, placebo-controlled, multi-centre studies in adults with a diagnosis of schizophrenia according to DSM-5 criteria.

The primary efficacy measure was the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at week five. The PANSS is a 30-item scale that measures symptoms of schizophrenia. Each item is rated by a clinician on a seven-point scale.

In both studies, the participants who received Cobenfy experienced a meaningful reduction in symptoms from baseline to week five compared to the placebo group.

Addressing a tolerability challenge

Cobenfy was initially invented by PureTech by combining two biologically active molecules – xanomeline and trospium chloride – to address a tolerability challenge that had held back a potential new class of medicines for the treatment of neuropsychiatric conditions.

In response to the FDA approval, PureTech received $29 million under agreements with Royalty Pharma and PureTech’s founded entity, Karuna Therapeutics, which was acquired by Bristol Myers Squibb (BMS) in March 2024.

Under these agreements, PureTech is also entitled to potential future payments as well as approximately 2% royalties on net annual sales over $2 billion.

Eric Elenko, Co-Founder and President of PureTech said: “Our initial hypothesis was that we could overcome the tolerability issues that had hindered the development of an otherwise promising drug, xanomeline, and we were able to test and validate this concept early on. We are immensely proud that our dedication to this programme has led to the first major innovation in decades for those living with schizophrenia. Congratulations to the teams at Karuna and BMS on this historic accomplishment.”

PureTech is currently developing LYT-100 (deupirfenidone) for the treatment of idiopathic pulmonary fibrosis (IPF) and anticipates topline data from a Phase IIb clinical trial by the end of the year.

Diana Spencer, Senior Digital Content Editor, DDW