The U.S. Food and Drug Administration (FDA) has approved Cobenfy (xanomeline/trospium chloride), a new medication offering a novel approach to treating schizophrenia, marking the first new type of schizophrenia drug in decades. Cobenfy, developed by Bristol Myers Squibb, aims to alleviate the hallucinations and "voices" associated with the disorder without the common side effects of existing medications, such as weight gain and lethargy.
Schizophrenia affects approximately 1 per cent of the global population and is a leading cause of disability worldwide. This severe and chronic mental illness is characterized by intrusive thoughts, hallucinations, and paranoia, which can significantly impair daily living and social interactions. According to the FDA, the illness not only affects quality of life but also raises the risk of early mortality, with nearly 5 per cent of people with schizophrenia dying by suicide.
Existing treatments for schizophrenia primarily target dopamine receptors in the brain, which can help control symptoms but often lead to undesirable side effects like weight gain, lack of motivation, and sluggishness. These side effects have prompted many patients to discontinue their medications. In contrast, Cobenfy works indirectly on dopamine through cholinergic receptors, influencing the neurotransmitter acetylcholine instead. This new approach offers a promising alternative to the dopamine-focused antipsychotic medications that have been the mainstay of schizophrenia treatment for decades.
“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 Dr Tiffany Farchione, director of psychiatry in the Office of Neuroscience at the FDA’s Center for Drug Evaluation and Research. “This drug takes the first new approach to schizophrenia treatment in decades, offering a new alternative to the antipsychotic medications people with schizophrenia have previously been prescribed.”
Cobenfy’s approval was based on the results of two five-week double-blind trials in which neither the patients nor the healthcare providers knew whether participants were receiving the drug or a placebo. The studies measured patient outcomes using a standard 30-item scale assessing schizophrenia symptoms. According to the FDA, participants who received Cobenfy experienced a significant reduction in symptoms compared to those given a placebo.
However, like all medications, Cobenfy comes with potential side effects, including gastrointestinal issues such as nausea, indigestion, constipation, and vomiting. The drug may also cause an increased heart rate and acid reflux. Due to the risk of liver damage, Cobenfy is not recommended for individuals with pre-existing liver impairments.
Notably, Cobenfy does not have the boxed warning often required for other antipsychotic medications, reflecting its different risk profile. Still, the trials only spanned five weeks, leaving questions about its long-term effectiveness and safety. “We don’t know how it works in any substantial way past five weeks,” said Dr David Rind, medical director of the Institute for Clinical and Economic Review. Concerns remain about potential long-term neurological effects, such as motor disorders.
Bristol Myers Squibb has conducted individual case studies of patients who have taken Cobenfy for up to a year, reportedly showing no metabolic changes or movement disorders. The company plans to publish these results later in 2024, which may provide further insight into the drug's long-term safety.