FDA Approves Schizophrenia Treatment that Targets Cholinergic Receptors

On Sept. 26, 2024, FDA announced that the agency has approved Bristol Myers Squibb’s (BMS) Cobenfy (xanomeline and trospium chloride) capsules to treat schizophrenia in adults. The approval is significant because it is the first treatment for schizophrenia that targets cholinergic receptors. The standard treatments target dopamine receptors.

The approval was based on results from two identical studies; both were five-week studies that were randomized, double-blind, placebo-controlled, and multi-centered. Study participants were adults diagnosed with 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 5. 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 5 as measured by the PANSS Total Score compared to the placebo group,” FDA stated in the press release (1).

According to FDA, symptoms of schizophrenia include “hallucinations, difficulty controlling one’s thoughts, and being suspicious of others.” Patients may also have cognitive problems and difficulty with social interactions. Schizophrenia impacts approximately 1% of Americans and is one of the 15 leading causes of disability worldwide (2). Schizophrenia also poses a greater risk of death at a young age.

“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, in a press release. “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.”

“Today’s landmark approval of our first-in-class treatment for schizophrenia marks an important milestone for the community, where after more than 30 years, there is now an entirely new pharmacological approach for schizophrenia—one that has the potential to change the treatment paradigm,” said Chris Boerner, PhD, board chair and chief executive officer at BMS, in a company press release (3). “As we reenter the field of neuropsychiatry, we are dedicated to changing the conversation around serious mental illness, beginning with today’s approval in schizophrenia.”

“For people living with schizophrenia, it's often difficult to find a treatment that works for them. Having a variety of treatment options gives patients and healthcare providers the tools to help manage this serious condition,” said Gordon Lavigne, chief executive officer of the Schizophrenia & Psychosis Action Alliance, in the BMS press release (3). “People living with schizophrenia want and deserve more. Today's approval provides a new option as people with schizophrenia move forward with proper support to rebuild their lives.”

“Due to its heterogeneous nature, schizophrenia is not a one-size-fits-all condition, and people often find themselves in a cycle of discontinuing and switching therapies,” said Rishi Kakar, MD, chief scientific officer and medical director at Segal Trials and investigator in the EMERGENT program, in the press release (3). “The approval of C[obenfy] is a transformative moment in the treatment of schizophrenia because, historically, medicines approved to treat schizophrenia have relied on the same primary pathways in the brain. By leveraging a novel pathway, C[obenfy] offers a new option to manage this challenging condition.”

Cobenfy, however, may cause urinary retention, and should not be prescribed to patients with urinary retention, according to FDA. There is also the possibility of increased heart rate, decreased gastric movement, or angioedema (swelling) of the face and lips. Liver damage is also a risk and, therefore, the drug is not recommended for patients with liver impairment. Patients with moderate to severe renal impairment should also avoid the drug as it is substantially excreted by the kidneys.

Common side effects include nausea, indigestion, constipation, vomiting, hypertension, abdominal pain, diarrhea, increased heartbeat, dizziness, and gastroesophageal reflux disease.

References

1. FDA. FDA Approves Drug with New Mechanism of Action for Treatment of Schizophrenia. Press Release. Sept. 26, 2024.
2. NIMH. Schizophrenia. NIMH.NIH.gov (accessed Sept. 27, 2024). https://www.nimh.nih.gov/health/statistics/schizophrenia
3. BMS. US Food and Drug Administration Approves Bristol Myers Squibb’s COBENFY (xanomeline and trospium chloride), a First-In-Class Muscarinic Agonist for the Treatment of Schizophrenia in Adults. Press Release. Sept. 26, 2024.