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Bristol Myers Squibb have announced new interim results from the Phase 3 EMERGENT-4 open-label extension trial evaluating the long-term efficacy, safety and tolerability of KarXT (xanomeline-trospium) in adults with schizophrenia. Long-term efficacy data from the trial were presented in a poster titled, “Maintenance of Efficacy of KarXT (Xanomeline and Trospium) in Schizophrenia” (Poster F264) at the Annual Congress of the Schizophrenia International Research Society (SIRS) being held April 3-7, 2024, in Florence, Italy.
“We are pleased to see a continued and consistent meaningful reduction in symptoms of schizophrenia across 52-weeks in an outpatient setting, beyond what was seen in the short-term, in-patient five-week trials (EMERGENT-2 and EMERGENT-3),” said Roland Chen, MD, senior vice president and head, Immunology, Cardiovascular and Neuroscience development, Bristol Myers Squibb. “We look forward to continued conversations with the FDA and to sharing additional data from the EMERGENT program later this year.”
EMERGENT-4 is a Phase 3, 52-week, outpatient, open-label extension study evaluating the long-term safety, tolerability, and efficacy of KarXT in adults with schizophrenia who previously completed the treatment period of one of the Phase 3, five-week, double-blind, placebo-controlled, efficacy and safety studies, EMERGENT-2 or EMERGENT-3. At the time of the data cutoff of April 17, 2023, 110 patients were part of the interim efficacy analysis, with 29 patients having completed 52 weeks of treatment.
In the interim analysis, KarXT was associated with significant improvement in symptoms of schizophrenia across all efficacy measures at 52 weeks. At the end of the open-label extension, more than 75% of participants achieved >30% improvement in symptoms, with an average reduction of 33.3-points from baseline (98.4), as measured by the Positive and Negative Syndrome Scale (PANSS) total score. In addition, participants had a mean 1.7-point change in Clinical Global Impression-Severity (CGI-S) score from baseline (5.2), representing an average shift from ‘markedly ill’ at baseline to ‘moderately’ or ‘mildly’ ill at one year.
Improvements in symptoms of schizophrenia continued throughout the 52-week trial regardless of whether participants were previously treated with KarXT or placebo during the acute trials. Prior to enrolling in the open-label extension, participants who previously received placebo in EMERGENT-2 and EMERGENT-3 had a significantly higher mean PANSS total score compared to those who received KarXT (placebo 86.5 vs. KarXT 76.1). When dosed with KarXT, the patients previously on placebo had significant improvements in symptoms within two weeks of treatment with KarXT. After four weeks, PANSS total scores were comparable between those who received KarXT or placebo in the acute trials.
“These interim data from EMERGENT-4 continue to validate the potential of KarXT in the long-term management of schizophrenia, with continued benefit across 52 weeks of treatment,” said Elan Cohen, Ph.D., principal investigator, CenExel Hassman Research Institute and investigator in the EMERGENT program. “The consistency of efficacy results across all EMERGENT clinical trial programs is encouraging and suggest KarXT could provide a differentiated treatment approach for people living with schizophrenia.”
In additional data presented at the congress, KarXT demonstrated a favorable impact on weight and long-term metabolic profile where most patients experienced stability or improvements on metabolic parameters over 52 weeks of treatment. In long-term trials, KarXT was generally well tolerated, with a side effect profile consistent with prior trials of KarXT in schizophrenia. KarXT was not associated with significant changes related to prolactin or clinically meaningful changes in movement disorder scale scores over 52 weeks (Oral Session: New Pharmacological Treatments and Assessments and Poster F74).