Xanomeline, combined with trospium chloride, has demonstrated consistent efficacy in treating schizophrenia, according to pooled results from three Phase 3 EMERGENT trials. The analysis, encompassing data from studies conducted in the United States and Ukraine, reveals significant improvements in both positive and negative symptoms of schizophrenia, offering a potential new treatment option for this challenging condition.
Consistent Efficacy Across Multiple Trials
The pooled analysis included data from adults aged 18-65 with a primary diagnosis of schizophrenia, confirmed by the Mini International Neuropsychiatric Interview. Participants had experienced an acute exacerbation of psychotic symptoms requiring hospitalization within two months of screening and were free of oral antipsychotics for at least one week prior to the baseline assessment. The trials were 5-week, multisite, inpatient, randomized, double-blind, placebo-controlled studies.
The primary endpoint was the change from baseline to week 5 in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary endpoints included changes in PANSS positive and negative subscales, the PANSS Marder negative factor, CGI-S score, and responder rates based on CGI-S and PANSS criteria. Xanomeline/trospium was administered twice daily, starting at 50mg xanomeline/20mg trospium and potentially increasing to 125mg xanomeline/30mg trospium based on tolerability.
Significant Symptom Reduction
The results showed a statistically significant improvement in PANSS total scores in the xanomeline-trospium group compared to placebo. This improvement was consistent across the PANSS positive and negative subscales, indicating a broad impact on the core symptoms of schizophrenia. The CGI-S scores also showed significant improvement, reflecting an overall reduction in the severity of the illness.
Subgroup Analysis
Subgroup analyses were conducted to assess the consistency of treatment effects across different patient populations. The subgroups were stratified by age (<45 years or ≥45 years), sex, race (Black or White), ethnicity (Hispanic/Latino or not Hispanic/Latino), country (United States or Ukraine), baseline body mass index (BMI; <30 kg/m2 or ≥30 kg/m2), and baseline PANSS total score (<95 or ≥95). The results indicated that xanomeline-trospium was effective across all subgroups, suggesting a broad applicability of the treatment.
Responder Rates
Responder analyses, based on a ≥30% improvement in PANSS total score, demonstrated clinically meaningful response rates in the xanomeline-trospium group compared to placebo. Additional response thresholds of ≥20%, ≥40%, and ≥50% were also assessed, with consistent trends favoring the active treatment. Similarly, CGI-S responder analysis, based on ≥1-point, ≥2-point, and ≥3-point improvements, showed higher response rates in the xanomeline-trospium group.
These findings support the potential of xanomeline-trospium as a valuable addition to the treatment armamentarium for schizophrenia, addressing both positive and negative symptoms with a consistent effect across diverse patient subgroups.
