REMISSION WITH LUMATEPERONE 42 MG ADJUNCTIVE TO ANTIDEPRESSANT THERAPY IN PATIENTS WITH MAJOR DEPRESSIVE DISORDER: ANALYSIS OF SHORT-TERM AND LONG-TERM TRIALS

Background

Lumateperone is an atypical antipsychotic indicated for: treatment of schizophrenia in adults; treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) in adults, as monotherapy and as adjunctive therapy with lithium or valproate; and treatment of major depressive disorder (MDD) in adults as adjunct to antidepressant therapy (ADT). This analysis of 2 Phase 3, randomized, double-blind, placebo-controlled studies (Study 501 [NCT04985942]; Study 502 [NCT05061706]) and open-label extension study (OLE; Study 503 [NCT05061719]) evaluated MontgomeryAsberg Depression Rating Scale (MADRS) Total score remission rates in patients with MDD with inadequate ADT response.

Methods

Studies 501and 502 enrolled adults with DSM-5 criteria for MDD with inadequate response to 1-2 ADTs in current depressive episode, MADRS Total score ≥24, Clinical Global Impression-Severity score ≥4, and Quick Inventory of Depressive SymptomatologySelf Report-16 item score ≥14. Patients were randomized 1:1 to 6-week placebo+ADT or lumateperone 42mg+ADT. Those completing double-blind treatment could enroll in Study 503 to receive 26-week lumateperone 42mg+ADT. Efficacy was evaluated in overall populations and patient subgroups using logistic regression (pooled 501/502) and descriptive statistics (503). MADRS remission (MADRS Total score ≤10), complete remission (MADRS Total score ≤5), and sustained remission (MADRS Total score ≤10 through end of treatment) were assessed.

Results

The modified intent-to-treat population comprised 950 patients (lumateperone+ADT, n=471; placebo+ADT, n=479) in 501/502; 809 were enrolled in 503. In 501/502, MADRS Total score remission rates at Day 43 were significantly greater with lumateperone+ADT vs placebo+ADT (25.5% vs 13.6%; P < .0001), and remission occurred in 529 (65.4%) patients at end of OLE (Study 503). Compared with placebo+ADT, there were significantly greater MADRS remission rates at Day 43 with lumateperone+ADT in patient subgroups in 501/502, higher complete remission rate (10.6% vs 5.6%; P < .01), and significantly greater sustained remission rates, from Day 22 (6.2% vs 2.9%; P < .05) through to Day 43 (25.5% vs 13.6%; P < .0001). In 503, lumateperone+ADT resulted in high MADRS remission rates across patient subgroups. Complete remission was achieved by 44.1% of patients by end of open-label treatment, with sustained remission rates reaching 60.4% by Week 26.

Conclusion

Lumateperone 42mg+ADT demonstrated significantly greater remission rates over placebo+ADT in pooled short-term studies of patients with MDD with inadequate ADT response, with two-thirds achieving remission with 6-month treatment, supporting lumateperone as a promising adjunctive treatment.