Karuna Therapeutics’ Cobenfy Receives Green Light from FDA, Offering Hope to Schizophrenia Patients

On September 26, a significant milestone was reached in the treatment of schizophrenia, as the U.S. Food and Drug Administration (FDA) granted approval for Cobenfy, marking the first new treatment for the disorder in nearly 30 years. Developed by Karuna Therapeutics and later acquired by Bristol Myers Squibb, Cobenfy offers a novel mechanism of action, sparking excitement among both medical professionals and patients.

Unlike existing schizophrenia medications that primarily target the dopamine neurotransmitter system, Cobenfy focuses on the cholinergic system, specifically through muscarinic receptors. This innovative approach stems from earlier research at Eli Lilly, where scientists noted that manipulating the muscarinic system appeared to alleviate some symptoms of Alzheimer’s-related psychosis. However, challenges arose due to the widespread presence of these receptors throughout the body, leading to undesirable side effects. Researchers subsequently halted their investigations.

Karuna co-founder Andrew Miller revisited this concept and sought to selectively activate the muscarinic system in the brain while minimizing side effects in other body parts. After testing approximately 7,000 compounds, Miller and his team successfully combined xanomeline—a compound linked to the muscarinic system—with a drug approved in the 1970s for treating overactive bladder. This combination led to the development of Cobenfy, previously known as KarXT.

Clinical studies published in the journal *Lancet* demonstrated that Cobenfy significantly alleviated schizophrenia symptoms such as hallucinations and paranoia compared to a placebo. These promising results contributed to Bristol Myers Squibb’s decision to acquire Karuna in 2023. According to Adam Lenkowsky, Chief Commercialization Officer at Bristol Myers Squibb, the company sought a transformative asset that could offer a different mechanism of action from traditional dopamine-based treatments.

Dr. Rishi Kakar, Chief Scientific Officer at Segal Trials, emphasized the unique mechanism of action of Cobenfy, which may benefit the estimated 60% of schizophrenia patients who do not respond well to existing treatments. The trials included patients who had stopped their previous medications due to intolerable side effects, and results showed a substantial reduction in symptoms for those receiving Cobenfy.

While Cobenfy is approved as a standalone treatment, further studies will explore its effectiveness when combined with existing medications. Side effects reported during trials were generally mild, including nausea and gastrointestinal distress, and were mostly transient. However, the drug is not recommended for individuals with a history of liver or kidney disorders.

The wholesale cost of Cobenfy is set at $1,850 per month, although insurance may lower this for many patients. With approximately 80% of U.S. schizophrenia patients covered by Medicare or Medicaid, access to this groundbreaking treatment may become a reality for many.

Bristol Myers Squibb plans to expand research on Cobenfy, with investigations into its potential applications for other neurological conditions, including Alzheimer’s-related psychosis and bipolar disorder. This innovation represents a promising step forward in neuropsychiatry, potentially paving the way for a new generation of effective treatments.