Data from the EMERGENT-4 and EMERGENT-5 Phase III trials, presented at the 2024 Psych Congress, reveal that Cobenfy (xanomeline and trospium chloride) maintains long-term efficacy in treating schizophrenia in adult patients over a 52-week period. The trials demonstrated significant improvements in schizophrenia symptoms and quality of life with minimal adverse effects.
Sustained Symptom Improvement
The EMERGENT-4 trial, a 52-week open-label extension, assessed the long-term safety, tolerability, and efficacy of Cobenfy in 156 adults with schizophrenia. These patients had previously completed the EMERGENT-2 or EMERGENT-3 trials. Results showed sustained improvements across all efficacy benchmarks, including the Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity (CGI-S) score, and PANSS subscale scores.
Patients initially assigned to the placebo group in the acute trials experienced rapid symptom improvement upon starting Cobenfy. By the end of the 52-week extension, 69% of patients completing the study achieved a ≥30% improvement in schizophrenia symptoms from the acute trial baseline, as measured by the PANSS total score.
Efficacy in Patients with Stable Symptoms
The EMERGENT-5 trial, also a 52-week open-label study, evaluated the long-term effects of Cobenfy in 566 adult patients with schizophrenia who had stable symptoms on prior antipsychotic therapy and no prior exposure to Cobenfy. Patients enrolled had a PANSS total score ≤80 (mean 66.0) and a CGI-S score ≤4 (mean 3.4), indicating mild to moderate illness.
After 52 weeks, patients treated with Cobenfy showed improvements in schizophrenia symptoms across all efficacy measures, including PANSS total, CGI-S, and PANSS subscale scores. Thirty percent of patients achieved a ≥30% reduction from baseline in the PANSS total score, with an average reduction of -5.5 points from baseline at 52 weeks. These results confirm the maintenance of effect with long-term treatment.
Safety and Tolerability
Cobenfy was well-tolerated in both trials, with no new safety signals reported. Pooled data from EMERGENT-4 and EMERGENT-5 indicated that 65% of patients experienced weight loss. No significant changes were observed in total cholesterol, triglycerides, or HbA1c levels. Common adverse events included nausea, vomiting, constipation, dry mouth, dyspepsia, dizziness, hypertension, and diarrhea.
Clinical Implications
"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," said Alyssa Johnsen, MD, PhD, Senior Vice President and Head of Clinical Development, Immunology, Cardiovascular and Neuroscience, Bristol Myers Squibb. She also noted the compelling safety and tolerability profile associated with long-term Cobenfy treatment, consistent with prior studies, and the lack of weight gain, movement disorders, or metabolic changes.
Schizophrenia, affecting approximately 0.3% of the global population and an estimated 2.8 million people in the United States, often requires lifelong treatment. Cobenfy offers a novel mechanism of action and a distinct profile, potentially improving long-term outcomes for patients with schizophrenia.
