Long-Term Metabolic Outcomes associated with KarXT (Xanomeline and Trospium): Interim Results from Pooled, Long-Term Safety Studies EMERGENT-4 and EMERGENT-5
Current schizophrenia treatments often cause metabolic disturbances. KarXT, an investigational medication combining xanomeline, a muscarinic receptor agonist, and trospium chloride, a muscarinic receptor antagonist, has shown efficacy and safety in the 5-week, randomized, double-blind, placebo-controlled EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials and was not associated with weight gain or adverse metabolic effects. KarXT is being evaluated in the Phase 3, 52-week, outpatient, open-label EMERGENT-4 and EMERGENT-5 trials.
EMERGENT-4 and EMERGENT-5 trials included participants with schizophrenia, continuing from short-term trials (EMERGENT-4) or with stable symptoms (EMERGENT-5). Participants received KarXT starting at 50mg/20mg twice daily (BID), increasing to 125 mg/30mg BID. Data from both trials were pooled for safety analysis, with 275 subjects ongoing at the data cut.
Baseline measurements indicated some metabolic dysfunction which is fairly typical for the schizophrenia population (mean BMI: 29.7; HbA1c: 5.8%). Participants had a mean weight change of -1.7kg after 24-weeks of KarXT and -2.7kg after 52 weeks. More participants experienced potentially clinically significant (PCS) decreases in weight (≥7% decrease) versus PCS increases in weight (≥7% increase) over the course of treatment. Cholesterol remained stable (+0.0mg/dL after 24 weeks and +3.09mg/dL after 52 weeks), and fewer participants had PCS high cholesterol at their last assessment. Mean triglycerides decreased over the course of treatment and HbA1c remained stable.
Interim findings from pooled, long-term studies provide evidence KarXT treatment is not associated with long-term metabolic disturbances in participants with schizophrenia. KarXT demonstrates a favorable long-term metabolic profile, with participants showing improvements or stability in metabolic parameters over 52 weeks.
