FDA Approves Bristol Myers Squibb’s Cobenfy for Schizophrenia

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The FDA has approved Bristol Myers Squibb’s Cobenfy (xanomeline and trospium chloride) for treating schizophrenia in adults. According to the company, this marks the first new class of medication for schizophrenia approved by the FDA in decades. Approval was based on data from three placebo-controlled efficacy trials and two open-label safety studies in the EMERGENT clinical program, including the Phase III EMERGENT-2 and EMERGENT-3 trials.¹

“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, CEO, Bristol Myers Squibb, in a press release. “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.”

Bristol Myers Squibb acquired Cobenfy, formerly known as KarXT, after reaching a definitive merger agreement with Karuna Therapeutics in December 2023 for a total equity value of $14.0 billion.²

The EMERGENT-2 and EMERGENT-3 trials were five-week, inpatient trials that evaluated the efficacy, safety, and tolerability of Cobenfy compared to placebo in adults with schizophrenia. The primary endpoint of both studies was a statistically significant reduction of schizophrenia symptoms compared to placebo as measured by the Positive and Negative Syndrome Scale (PANSS) total score change from baseline to week five. The secondary endpoint of the trials was a statistically significant improvement in illness from baseline to week five, as measured by the Clinical Global Impression-Severity (CGI-S) score.

Results found that Cobenfy demonstrated a 9.6-point reduction (-21.2 Cobenfy vs. -11.6 placebo, p<0.0001) and an 8.4-point reduction (-20.6 Cobenfy vs. -12.2 placebo; p<0.0001) in PANSS total score compared to placebo at week five in EMERGENT-2 and EMERGENT-3, respectively. Further, Cobenfy met the secondary endpoint in the EMERGENT-2 trial.

Common adverse events (AEs) associated with Cobenfy were gastrointestinal-related, including nausea, dyspepsia, and constipation. Other common AEs included hypertension, diarrhea, dyspepsia, abdominal pain, tachycardia, dizziness, and gastroesophageal reflux disease. The safety and tolerability profile of the treatment has been established across acute and long-term trials.¹

“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, CEO, Schizophrenia & Psychosis Action Alliance, in the press release. “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.”

The National Alliance on Mental Illness estimates that anywhere from 0.25% to 0.64% of adults in the United States are currently living with schizophrenia. While it can begin at any age, it is most common in the late teens to the early twenties for men, and the late twenties to early thirties for women. Notably, it is uncommon for patients under the age of 12 years or over 40 years to be diagnosed with schizophrenia.³

“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, medical director, Segal Trials, investigator in the EMERGENT program, in the press release. “The approval of Cobenfy 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, Cobenfy offers a new option to manage this challenging condition.”

References

1. U.S. 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. BMS. September 26, 2024. Accessed September 27, 2024. https://news.bms.com/news/details/2024/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-COBENFY-xanomeline-and-trospium-chloride-a-First-In-Class-Muscarinic-Agonist-for-the-Treatment-of-Schizophrenia-in-Adults/default.aspx

2. Bristol Myers Squibb Strengthens Neuroscience Portfolio with Acquisition of Karuna Therapeutics. News release. Bristol Myers Squibb. December 22, 2023. Accessed September 27, 2024. https://news.bms.com/news/corporate-financial/2023/Bristol-Myers-Squibb-Strengthens-Neuroscience-Portfolio-with-Acquisition-of-Karuna-Therapeutics/default.aspx

3. Schizophrenia. NAMI. Accessed September 27, 2024. https://www.nami.org/about-mental-illness/mental-health-conditions/schizophrenia/#:~:text=The%20exact%20prevalence%20of%20schizophrenia,to%20early%2030s%20for%20women.