Phase III Trials Show Long-Term Efficacy of Cobenfy Treating Schizophrenia

Credit: Olivier Le Moal | stock.adobe.com

Data from a pair of Phase III trials presented at the 2024 Psych Congress demonstrate that Cobenfy (xanomeline and trospium chloride) maintained long-term efficacy in adult patients with schizophrenia over 52 weeks, producing significant improvements in symptoms and quality of life with minimal adverse effects (AEs).¹ Cobenfy, formerly called KarXT, is an oral muscarinic antipsychotic currently indicated to treat schizophrenia in adult patients.

“The results from our long-term trials further support the differentiated profile of Cobenfy and reinforce prior findings of robust and maintained symptom reduction with long-term treatment,” Alyssa Johnsen, MD, PhD, senior vice president and head of clinical development, Immunology, Cardiovascular and Neuroscience, Bristol Myers Squibb, said in a press release. “We’re pleased to see a compelling safety and tolerability profile associated with long-term Cobenfy treatment that is consistent with prior studies. Additionally, we continue to see a lack of weight gain, movement disorders, or metabolic changes with long-term use, reiterating the distinct profile and unique mechanism of action of Cobenfy. With Cobenfy now available for adults with schizophrenia, we look forward to further understanding the real-world impact of this differentiated treatment option.”¹

Schizophrenia can be a disabling condition, potentially causing a combination of hallucinations, delusions, and extremely disordered thinking and behavior that has a negative impact on the patient’s ability to function in daily life. As such, patients with schizophrenia require lifelong treatment; however, treatment initiated early after diagnosis may help to get the symptoms under control prior to the development of serious complications, which may improve long-term outlook for patients. Schizophrenia is estimated to affect approximately 0.3% of the global population and an estimated 2.8 million patients in the United States.²

The 52-week, outpatient, open-label EMERGENT-4 extension trial analyzed the long-term safety, tolerability, and efficacy of Cobenfy in 156 adult patients with schizophrenia who completed treatment in either of the Phase III, five-week, double-blind, placebo-controlled, EMERGENT-2 or EMERGENT-3 trials. Over the 52-week extension, investigators observed sustained improvements in the symptoms of schizophrenia across all efficacy benchmarks, which include Positive and Negative Syndrome Scale (PANSS) total, Clinical Global Impression-Severity (CGI-S), PANSS positive subscale, and PANSS negative subscale scores.

Patients randomly assigned to the placebo cohort in the acute trials showed a rapid improvement in symptoms after starting treatment with Cobenfy. After four weeks, PANSS total scores were comparable among those administered Cobenfy and placebo during the acute trials, according to the investigators.

Symptom improvements were sustained for the duration of the 52-week extension trial regardless of whether patients were administered Cobenfy or placebo during the acute trials. By completion of the 52-week extension trial, 69% of patients who finished the study achieved ≥30% improvement in schizophrenia symptoms from acute trial baseline, per PANSS total score.

The 52-week, outpatient, open-label EMERGENT-5 trial analyzed the long-term safety, tolerability, and efficacy of Cobenfy in 566 adult patients with schizophrenia who achieved stable symptoms on prior antipsychotic therapy and who had no previous exposure to Cobenfy. Eligibility criteria included a PANSS total score ≤80 (mean 66.0), a CGI-S score ≤4 (mean 3.4), and being considered mild to moderately ill.

At 52 weeks, patients administered Cobenfy achieved improvements in the symptoms of schizophrenia across all efficacy measures, including PANSS total, CGI-S, PANSS positive subscale, and PANSS negative subscale scores. Investigators stated that these findings confirm the maintenance of effect with long-term treatment. Thirty percent of patients had a ≥30% reduction from baseline in the PANSS total score, showing an average reduction of -5.5-points from baseline at 52 weeks.

In terms of safety, Cobenfy was found to be well-tolerated, with no new safety or tolerability signals reported. Pooled data released in April 2024 from EMERGENT-4 and EMERGENT-5 show that 65% of patients experienced weight loss, while no significant changes were observed in total cholesterol, triglycerides, and HbA1c levels. Common AEs included nausea, vomiting, constipation, dry mouth, dyspepsia, dizziness, hypertension, and diarrhea.³

References

1. Bristol Myers Squibb Presents New Long-term Data from the EMERGENT Program Evaluating COBENFY™ (xanomeline and trospium chloride) in Adults with Schizophrenia at Psych Congress 2024. News release. Bristol Myers Squibb. October 31, 2024. Accessed November 1, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Presents-New-Long-term-Data-from-the-EMERGENT-Program-Evaluating-COBENFY-xanomeline-and-trospium-chloride-in-Adults-with-Schizophrenia-at-Psych-Congress-2024/default.aspx

2. Schizophrenia. Mayo Clinic. Webpage. Updated January 7, 2020. Accessed November 1, 2024. https://www.mayoclinic.org/diseases-conditions/schizophrenia/symptoms-causes/syc-20354443

3. Bristol Myers Squibb Presents New Interim Long-Term Efficacy Data from the EMERGENT-4 Trial Evaluating KarXT in Schizophrenia at the 2024 Annual Congress of the Schizophrenia International Research Society. Bristol Myers Squibb. April 6, 2024. Accessed November 1, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Presents-New-Interim-Long-Term-Efficacy-Data-from-the-EMERGENT-4-Trial-Evaluating-KarXT-in-Schizophrenia-at-the-2024-Annual-Congress-of-the-Schizophrenia-International-Research-Society/default.aspx