New pooled interim long-term safety and metabolic outcomes data from the EMERGENT program evaluating KarXT in schizophrenia presented at the 2024 annual congress of the Schizophrenia International Research Society.- BMS

 These data were presented in a poster titled, “Long-Term Safety of KarXT (Xanomeline and Trospium) in Schizophrenia” (Poster F74) and in the Oral Session “Long-Term Metabolic Outcomes Associated With KarXT (Xanomeline and Trospium): Interim Results From Pooled, Long-Term Safety Studies EMERGENT-4 and EMERGENT-5” at the Annual Congress of the Schizophrenia International Research Society (SIRS) being held April 3-7, 2024, in Florence, Italy.

“These long-term safety results and metabolic outcomes from the EMERGENT program are extremely encouraging, allowing us to further understand the tolerability profile of KarXT in people living with schizophrenia,” said Roland Chen, MD, senior vice president and head, Immunology, Cardiovascular and Neuroscience development, Bristol Myers Squibb. “It is promising to see that over one year of treatment, KarXT was not associated with burdensome side effects, specifically weight gain and metabolic dysfunction, as well as extrapyramidal symptoms, which underscores its potential to provide a meaningful and differentiated option for people living with schizophrenia.”

Pooled Interim Long-Term Metabolic Outcomes Associated with KarXT (EMERGENT-4 and EMERGENT-5) : The EMERGENT-4 and EMERGENT-5 trials are Phase III, outpatient, 52-week, open-label trials evaluating the safety, tolerability, and efficacy of KarXT in adults with schizophrenia. At the time of the data cutoff of August 18, 2023, the interim pooled data analysis included 718 patients who received at least one dose of KarXT, with 134 patients having completed one year of treatment.

In the pooled analysis KarXT demonstrated a favorable impact on weight and long-term metabolic profile where most patients experienced stability or improvements on key metabolic parameters over 52 weeks of treatment. The majority of patients (65%) experienced an overall reduction in weight over the course of the trial, with more patients (18%) experiencing potentially clinically significant ( greater than 7% change) decreases in weight vs. 4% of patients experiencing increases in weight ( greater than 7% change). In patients who completed 52 weeks of treatment with KarXT, an average reduction in weight of 2.6kg was observed, with a larger mean reduction in weight of 4.1kg observed in clinically obese patients (BMI > 30 kg/m2). Total cholesterol, triglyceride and HbA1c levels did not meaningfully change over one year of treatment.

Interim Long-Term Pooled Safety Outcomes Associated with KarXT (EMERGENT-4 and EMERGENT-5): In the long-term studies, KarXT was generally well-tolerated across 52 weeks of treatment, with a side effect profile consistent with prior trials of KarXT in schizophrenia. The overall discontinuation rate in the trial was 53% and primary reasons for discontinuation included withdrawn consent (19%), treatment-related adverse events (15%), participant lost to follow-up (8%), and participant failed to adhere to protocol requirements (7%). Across the long-term EMERGENT trials, 62% of participants reported at least one treatment-related adverse event. The most common treatment-related adverse events ( greater than 5%) were nausea, vomiting, constipation, dry mouth, dyspepsia, dizziness, hypertension, and diarrhea, of which nearly all were mild or moderate in severity and transient in nature. KarXT was not associated with significant changes related to prolactin or clinically meaningful changes in movement disorder scale scores over 52 weeks.

“People living with schizophrenia and their care partners have long carried the burden of the condition, with a lack of treatment options that adequately treat the symptoms of schizophrenia without common debilitating side effects. To see that the long-term tolerability profile of KarXT remains consistent with earlier studies, where the cholinergic side effects of KarXT remained mainly mild or moderate in severity, and were transient and resolving with continued treatment is very encouraging,” said Rishi Kakar, M.D., chief scientific officer and medical director of Segal Trials and investigator in the EMERGENT program. “These results are extremely promising and add to the growing body of data which suggest that, if approved, KarXT could provide a long-desired, differentiated treatment option for people living with schizophrenia.”

In additional interim long-term data presented at the congress, KarXT was associated with significant improvements in symptoms of schizophrenia across all efficacy measures at 52 weeks in the EMERGENT-4 trial. Improvements in symptoms of schizophrenia continued throughout the open-label extension regardless of whether participants were previously treated with KarXT or placebo during the acute trials, EMERGENT-2 or EMERGENT-3 (Poster F264).