Lumateperone in Pooled Late-Phase Schizophrenia Trials: Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed

Abstract: Background: Lumateperone is an FDA-approved antipsychotic to treat schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder as monotherapy and as adjunctive therapy with lithium or valproate. This post hoc analysis investigated the efficacy and tolerability of lumateperone in patients with schizophrenia via number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH). Methods: Data were pooled from 3 late-phase 4-6 week placebo-controlled studies of lumateperone 42 mg/day in adults with schizophrenia and an acute exacerbation of psychosis (Study 005 [NCT01499563], Study 301 [NCT02282761], Study 302 [NCT02469155]). NNT and NNH were calculated vs placebo for several different Positive and Negative Syndrome Scale [PANSS] Total score response cutoffs (percent reduction from baseline) and for adverse events (AEs), respectively. Results: In the 2 informative studies (placebo, n=221; lumateperone, n=224), the NNT vs placebo for lumateperone was statistically significant for PANSS Total score reductions from baseline to 4-weeks/endpoint of ≥20% (NNT=9, 95% confidence interval [CI] 5-36) and ≥30% (NNT=8; 95%CI 5-21). In all studies pooled (placebo, n=412; lumateperone, n=406), study discontinuations due to AEs were uncommon and the NNH (389) was not statistically significant from placebo. The only AE with NNH vs placebo < 10 was somnolence/sedation (NNH=8; 95%CI 6-12). With lumateperone treatment, weight gain ≥7% from baseline was similar to placebo (NNH=112) and fewer patients experienced akathisia than placebo. Lumateperone LHH ratios were >>1 for all AEs (range 13.6-48.6) except somnolence/sedation (LHH~1). Conclusion: Lumateperone’s benefit-risk profile was favorable in late-phase schizophrenia trials.Short Description: In this post hoc analysis of late-phase trials of lumateperone 42 mg in patients with schizophrenia, the numbers needed to treat were favorable and statistically significant vs placebo while the numbers needed to harm vs placebo were >10 for most adverse events. Most likelihood to be helped or harmed ratios were >>1. These results demonstrate the efficacy of lumateperone 42 mg in treating schizophrenia without adverse effects on weight, motor function, or metabolic variables.Name of Sponsoring Organization(s): Intra-Cellular Therapies, Inc.