BMS gains approval for Karuna-acquired schizophrenia drug

The US Food and Drug Administration (FDA) has granted approval to Bristol Myers Squibb's groundbreaking schizophrenia medication, Cobenfy (xanomeline-trospium). This marks the introduction of a novel treatment option for patients, the first of its kind in decades.

Cobenfy's standout feature is its unique mechanism of action, targeting cholinergic receptors instead of the traditional dopamine receptors. The current market for schizophrenia treatments primarily consists of dopamine-blocking antipsychotics, which come with significant side effects such as Parkinsonian symptoms, sexual dysfunction, and weight gain. Cobenfy's approach offers a promising alternative by focusing on different receptors.

Originally developed by Karuna Therapeutics and named KarXT, the drug became part of Bristol Myers Squibb's portfolio following a substantial $14 billion acquisition finalized in March 2024. This acquisition is expected to be financially beneficial, with sales projections for Cobenfy reaching $2.99 billion by 2030, according to GlobalData forecasts.

Cobenfy is administered as a twice-daily pill, combining two drugs to target muscarinic receptors M1 and M4. These receptors play a role in increasing activity in the parasympathetic nervous system while mitigating side effects associated with their activation. Clinical trials have demonstrated that Cobenfy effectively alleviates symptoms such as delusions without some of the severe side effects seen with existing antipsychotics.

The drug's ability to address both positive and negative symptoms of schizophrenia has generated considerable excitement. While positive symptoms include hallucinations and delusions, negative symptoms encompass reduced emotional expression, speech, and motivation. Unlike dopamine receptors, M1 and M4 receptors target both types of symptoms.

Data from the Phase III EMERGENT-3 trial (NCT04738123) showed an 8.4-point reduction in Positive and Negative Syndrome Scale (PANSS) total score at week five compared to a placebo. Despite these promising results, Cobenfy, like all medications, has its own set of side effects. The prescribing information warns of potential issues including urinary retention, increased heart rate, decreased gastric movement, and angioedema (swelling beneath the skin) of the face and lips.

In an official statement, Tiffany Farchione, director of the Division of Psychiatry at the FDA’s Center for Drug Evaluation and Research, noted, “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.”

One point of concern among experts is the twice-daily dosing schedule, as consistent medication adherence can be particularly challenging for schizophrenia patients. However, during a Q1 2023 earnings call, Karuna’s former CEO Bill Meury expressed confidence that adherence to Cobenfy could surpass that of standard schizophrenia treatments.

To address the dosing frequency issue, Terran Biosciences is developing a prodrug version of xanomeline-trospium, named TerXT. Terran’s candidates aim to retain Cobenfy’s formulation while optimizing the dosing schedule to a more convenient once-daily oral regimen and a multi-month injectable form.

Bristol Myers Squibb also announced that patients could enroll in a support scheme known as the Cobenfy Cares program, set to be available in late October when the drug is expected to hit the market. The program aims to assist patients in accessing this new treatment option.