2026 ECNP Congress

PS01-1100

Lumateperone 42 mg in patients with major depressive disorder: analysis of remission in short- and long-term trials

Michael E. Thase — W.R. Earley, C. Chen, T. Escher, S. Durgam · Perelman School of Medicine- University of Pennsylvania, Psychiatry, Philadelphia, United States

2026 ECNP Congress

Background

Lumateperone is an atypical antipsychotic to treat schizophrenia, depressive episodes associated with bipolar I or II disorder, and major depressive disorder (MDD). This analysis of two Phase 3, randomized, double-blind, placebo-controlled studies (Study 501 [NCT04985942]; Study 502 [NCT05061706]) and an open-label extension study (OLE; Study 503 [NCT05061719]) evaluated Montgomery-Asberg Depression Rating Scale (MADRS) Total score remission rates in patients with MDD with inadequate antidepressant therapy (ADT) response.

Methods

Studies 501/502 randomized (1:1) patients with DSM-5 criteria for MDD with inadequate response to 1-2 ADTs in the current depressive episode to 6-week placebo+ADT or lumateperone 42mg+ADT. Those completing double-blind treatment could enrol in Study 503 to receive 26-week lumateperone 42mg+ADT. MADRS remission, complete remission, and sustained remission (MADRS Total score ≤10, ≤5, and ≤10, respectively) were assessed.

Results

The modified intent-to-treat (mITT) population comprised 950 patients (lumateperone+ADT, n=471; placebo+ADT, n=479) in pooled Studies 501/502; 809 patients were enrolled and treated with lumateperone+ADT in Study 503. In 501/502, MADRS Total score remission rates (lumateperone+ADT, 25.5%; placebo+ADT, 13.6%; P<.0001) were significantly greater with lumateperone+ADT vs placebo+ADT at Day 43. Remission occurred in 529 (65.4%) patients at end of open-label treatment in Study 503.

Significantly greater MADRS remission rates at Day 43 were observed in patient subgroups with lumateperone+ADT vs placebo+ADT in the pooled Studies 501/502: younger (age ≤40 years: lumateperone+ADT, n=42 [25.1%] vs placebo+ADT, n=19 [11.6%]; P<.01), older (age >40 years: n=78 [25.7%] vs n=46 [14.6%]; P<.001), selective serotonin reuptake inhibitor (SSRI) usage (n=91 [28.4%] vs n=48 [15.5%]; P<.0001), serotonin and norepinephrine reuptake inhibitor (SNRI)/other usage (n=29 [19.2%] vs n=17 [10.1%]; P<.05), baseline MADRS Total score <32 (n=85 [29.8%] vs n=46 [16.0%]; P<.001), and baseline MADRS Total score ≥32 (n=35 [18.8%] vs n=19 [9.9%]; P<.05). Complete remission was achieved by 50 patients (10.6%) with lumateperone+ADT and 27 patients (5.6%) with placebo+ADT (P<.01) in the pooled mITT population. Sustained remission rates were significantly greater with lumateperone+ADT vs placebo+ADT beginning at Day 22: Day 22 (n=27 [5.7%] vs n=14 [2.9%]; P<.05), Day 29 (n=49 [10.4%] vs n=28 [5.8%]; P<.05), Day 36 (n=79 [16.8%] vs n=43 [9.0%]; P<.001), and Day 43 (n=106 [22.5%] vs n=59 [12.3%]; P<.0001).

In Study 503, MADRS remission rates with lumateperone+ADT at end of treatment were analysed for subgroups based on: age (≤40 years: n=179 [67.3%]; >40 years: n=350 [64.5%]), type of ADT (SSRI: n=374 [69.9%]; SNRI/other: n=155 [56.6%]), and baseline severity (baseline MADRS Total score <32: n=338 [69.7%]; baseline MADRS Total score ≥32: n=191 [59.0%]). Complete remission was achieved by 357 patients (44.1%) in the OLE. Sustained remission rates were: Week 1 (n=107 [13.2%]), Week 8 (n=231 [28.6%]), Week 16 (n=301 [37.2%]), Week 24 (n=330 [40.8%]), and end of open-label treatment (n=346 [42.8%]).

Conclusions

Two-thirds of patients achieved remission with 6-month adjunctive lumateperone treatment, supporting lumateperone as adjunctive therapy in patients with MDD with inadequate ADT response.

References

No references