Lumateperone Significantly Enhances Antidepressant Effects in Phase 3 Trial

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Taking lumateperone daily alongside antidepressants significantly reduces depression symptoms in patients with major depressive disorder (MDD), a phase 3 trial found.

The US Food and Drug Administration (FDA) has previously approved lumateperone for the treatment of schizophrenia and a monotherapy or an adjunctive therapy with lithium or valproate for bipolar depression. Positive topline results show lumateperone can also be an effective adjunctive therapy for patients with MDD.

Intra-Cellular Therapies announced on June 18, 2024 the second phase 3 trial evaluating lumateperone 42 mg adjunctive therapy in patients with MDD met the primary endpoint of change from baseline at Week 6 on the Montgomery-Åsberg Depression Scale (MADRS) total score versus placebo. The trial was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed-group study with 480 participants.

The participants were randomized 1:1 to lumateperone 42 mg alongside an antidepressant or placebo alongside an antidepressant to assess the efficacy and safety of lumateperone as an adjunctive treatment to antidepressants. Baseline MADRS total scores for patients on lumateperone 42 mg was 30.8 for the lumateperone group and 31.5 for the placebo group.

Participants on lumateperone had a 4.5-point reduction (P < .0001; Cohen’s d effect size = 0.56) on the MADRS total score, thus meeting the primary endpoint. Lumateperone 42 mg also met the key secondary endpoint of change from baseline at week 6 on the Clinical Global Impression Scale for Severity of Illness (CGI-S) P < .0001).

Improvement in the MADRS score was seen as early as Week 1 (P = .0504), and statistically significant separation on the CGI-S was observed beginning at Week 3.

Additionally, the efficacy of lumateperone was demonstrated in the Quick Inventory of Depressive Symptomatology Self-Report scale (P < .0001). This s a 16-item patient-related scale of symptom severity in depression, assessing symptoms of depression, insomnia/hyperinsomnia, low mood, appetite/weight changes, impaired self-perception, concentration difficulties, loss of interest/pleasure, suicidal ideation, psychomotor agitation, and fatigue.

Lumateperone demonstrated a favorable safety and tolerability profile, comparable to previous lumateperone trials. The most common adverse events—dizziness, somnolence, dry mouth, nausea, diarrhea, and fatigue—occurred more than double in patients on lumateperone than the adverse events in patients on placebo. Adverse events were mostly mild to moderate in severity and resolved during the study.

Intra-Cellular Therapies anticipates submitting a supplemental New Drug Application for the adjunctive treatment of MDD in the second half of 2024.

“We are confident that the efficacy results from Studies 501 and 502, along with the favorable safety and tolerability profiles from these studies, will make lumateperone a drug of choice for patients suffering with MDD who are having an inadequate response to antidepressant therapy,” said Sharon Mates, PhD, chairman and CEO of Intra-Cellular Therapies. “We are very pleased with the robust efficacy results from Study 502 which are consistent with the compelling results from Study 501. These results further support our vision for CAPLYTA to become a leading option for patients and providers across mood disorders.”

References

1. ^{Intra-Cellular Therapies Announces Positive Topline Results in Second Phase 3 Trial Evaluating Lumateperone as Adjunctive Therapy in Patients with Major Depressive Disorder. Intra-Cellular Therapies. June 18, 2024. https://ir.intracellulartherapies.com/news-releases/news-release-details/intra-cellular-therapies-announces-positive-topline-results-1. Accessed June 18, 2024.}
2. ^{Campbell, P. Lumateperone Receives FDA Approval for Schizophrenia in Adults. HCPLive. December 23, 2019. https://www.hcplive.com/view/lumateperone-fda-approval-schizophrenia-intra-cellular-therapies. Accessed June 18, 2024.}
3. ^{Walter, K. FDA Approves Lumateperone for Bipolar Depression. HCPLive. December 20, 2021. https://www.hcplive.com/view/fda-approves-lumateperone-bipolar-depression. Accessed June 18, 2024}