Bristol Myers Squibb Shares EMERGENT-4, EMERGENT-5 Results on Cobenfy for Schizophrenia

Bristol Myers Squibb announced on October 31, 2024, the new topline results from the phase 3 EMERGENT-4 and EMERGENT-5 open-label trials assessing the long-term efficacy, safety, and tolerability of xanomeline and trospium chloride (Cobenfy) over 52 weeks in adults with schizophrenia.¹ Investigators presented the findings at the 2024 Psych Congress in Boston.

Xanomeline trospium chloride capsules, approved by the US Food and Drug Administration (FDA) on September 26, 2024, demonstrated significant improvements in schizophrenia symptoms in the short and long term.² Once again in EMERGENT-4 and EMERGENT-5, results showed xanomeline and trospium chloride were linked to continued improvements in symptoms of schizophrenia.¹ In qualitative interviews during EMERGENT-5, participants reported quality of life improvements across physical, social, emotional, and role functioning.

“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 at Bristol Myers Squibb, in a statement.

Emergent-4 Findings

EMERGENT-4, a phase 3, 52-week, outpatient, open-label extension study, evaluated the long-term safety, tolerability, and efficacy of xanomeline trospium chloride in 156 adults with schizophrenia. Participants had previously completed the treatment period of EMERGENT 2 or EMERGENT-3—2 phase 3, 5-week, double-blind, placebo-controlled trials evaluating efficacy and safety.

In EMERGENT-4, participants continued receiving improvements in schizophrenia symptoms across all efficacy measures over 52 weeks, demonstrated by scores in the Positive and Negative Syndrome Scale (PANSS) total, Clinical Global Impression-Severity (CGI-S), PANSS positive subscale, and PANSS negative subscale scores.

Participants who had originally received a placebo in EMERGENT 2 or 3 demonstrated rapid improvement once they started xanomeline tropism chloride in EMERGENT-4. By week 4, investigators observed comparable PANSS total scores between participants who previously received xanomeline tropism chloride in the acute trials and those who had received a placebo. At the end of the study, 69% of participants achieved ≥ 30% improvement in schizophrenia symptoms from the acute trial baseline.

Like the previous trials, EMERGENT-4 demonstrated the safety and tolerability of xanomeline trospium chloride. Treatment-emergent adverse events, such as nausea, vomiting, dyspepsia, dry mouth, and hypertension, were mostly mild to moderate in intensity. The medication was linked to a mean change in body weight of -1.9 kg (±4.7 kg) from acute baseline to 52 weeks.

EMERGENT-5 Results

EMERGENT-5, a phase 3, 52-week, outpatient, open-label study, also assessed the long-term safety, tolerability, and efficacy of xanomeline trospium chloride, but this time with a sample of 566 adults with schizophrenia. Participants had stable symptoms on a previous antipsychotic but no exposure to xanomeline trospium chloride. At baseline, participants were considered mild to moderately ill, with a PANSS total score of ≤ 80 (mean: 66.0) and a CGI-S score ≤ 4 (mean 3.4).

After taking the xanomeline trospium chloride, participants had improved schizophrenia symptoms, measured by the PANSS total, CGI-S, PANSS positive subscale, and PANSS negative subscale scores at 52 weeks. At the end of the trial, 30% of participants had a ≥ 30% reduction from baseline in the PANSS total score, averaging a decrease of -5.5 points from baseline. EMEGRENT-5 once again showed xanomeline trospium chloride was safe and well-tolerated.

EMERGENT-5 also included in-trial interviews, conducted at 6 weeks (n = 70) and 6 months (n = 47). At 6 weeks, participants reported high satisfaction with the drug compared to their prior antipsychotic treatment. They also reported little burden linked to the treatment, contributing to their satisfaction. At 6 months, most participants (93%) reported they would recommend xanomeline trospium chloride to a friend or family member, and 78% said they would continue the drug after the trial.

“We’re pleased to see a compelling safety and tolerability profile associated with long-term COBENFY treatment that is consistent with prior studies,” Johnsen said. “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.”

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. Bristol Myers Squibb. October 31, 2024. https://news.bms.com/news/details/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. Accessed November 1, 2024.}
2. ^{Derman, C. FDA Approves Xanomeline and Trospium Chloride (Cobenfy) for Schizophrenia. HCPLive. September 26, 2024. https://www.hcplive.com/view/fda-approves-xanomeline-and-trospium-chloride-cobenfy-for-schizophrenia. Accessed November 1, 2024.}