Positive Phase 3 Results Evaluating Lumateperone for the Prevention of Relapse in Schizophrenia

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Intra-Cellular Therapies recently announced positive results from study 304 evaluating the efficacy and safety of lumateperone (Caplyta) 42 mg for the prevention of relapse in adult patients with schizophrenia.¹

“Schizophrenia is a chronic, serious mental illness characterized by the occurrence of acute psychotic episodes that cumulatively worsen disease prognosis. The control of symptoms and the prevention of relapses is critical to improving long-term patient outcomes. We are very pleased that the results from study 304, a randomized withdrawal trial, demonstrated efficacy along with favorable safety and tolerability which support the benefit of continued long-term treatment with lumateperone,” said Suresh Durgam, MD, executive vice president and chief medical officer of Intra-Cellular Therapies.¹

Study 304 was a multicenter, multi-national, randomized, double-blind, placebo-controlled, parallel group study evaluating lumateperone for the prevention of symptomatic relapse in adults with schizophrenia. During this 47-week study, there was an 18-week open-label phase where patients with schizophrenia were treated with lumateperone 42 mg per day, and those who met the stabilization criteria during that period progressed to the double-blind treatment phase. Patients were randomized to continue lumateperone 42 mg (N=114) or switched to placebo (N=114) for up to 26 weeks or until relapse occurred.

Lumateperone met the primary endpoint, which was time to first symptom relapse; time to relapse during the double-blind treatment phase was significantly longer in participants on lumateperone compared with those receiving placebo (P=0.0002). There were 18 relapses (16.4%) in the lumateperone group vs 44 relapses (38.6%) in the placebo group. Treatment with lumateperone was associated with a 63% reduction in risk of relapse vs placebo (hazard ratio [95% CI] = 0.37, [0.22, 0.65]).

The secondary endpoint was time to all cause discontinuation during the double-blind phase, and it was also met (P=0.0007), showing better treatment discontinuation rates during the double-blind phase.

As to safety profile, lumateperone was generally safe and well tolerated in this study. In the double-blind phase, the most commonly reported adverse event that was observed at a rate greater than or equal to 5% and twice the rate of placebo was headache.

Earlier this year, Intra-Cellular Therapies’ study 502 evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of major depressive disorder saw positive results.² Lumateperone 42 mg achieved statistically significant and clinically meaningful results in both the primary and the key secondary endpoints, robustly improved depressive symptoms as reported by patients as measured by the Quick Inventory of Depressive Symptomatology Self Report (P<0.0001), a 16-item patient-rated scale of symptom severity in depression that assesses 9 key symptoms. This study—as well as the positive phase 3 trial, study 501³—forms the basis for the lumateperone sNDA for the adjunctive treatment of MDD.

Another study, study 403, evaluated lumateperone 42 mg for adults aged 18 to 75 years who had received a DSM-5 diagnosis of either MDD or bipolar 1 or 2 disorder and were experiencing a major depressive episode with mixed features. Participants were randomized to receive either 42 mg of lumateperone or a placebo daily for 6 weeks. The primary measure of efficacy was the change in Montgomery-Åsberg Depression Rating Scale single-item scores, assessed at regular intervals. Safety was monitored through adverse events, Young Mania Rating Scale scores, and incidences of suicidality. The results of the study demonstrated that lumateperone significantly improves symptoms in this patient population, highlighting the efficacy and safety of the treatment compared with placebo.⁴

References

1. Intra-Cellular Therapies announces positive topline results in phase 3 trial evaluating Caplyta for the prevention of relapse in patients with schizophrenia. News release. November 5, 2024. Accessed November 6, 2024. https://www.globenewswire.com/news-release/2024/11/05/2974784/30597/en/Intra-Cellular-Therapies-Announces-Positive-Topline-Results-in-Phase-3-Trial-Evaluating-CAPLYTA-for-the-Prevention-of-Relapse-in-Patients-with-Schizophrenia.html

2. Kuntz L. Lumateperone as an adjunctive therapy to antidepressants: more positive results. Psychiatric Times. June 18, 2024. https://www.psychiatrictimes.com/view/lumateperone-as-an-adjunctive-therapy-to-antidepressants-more-positive-results

3. Kuntz L. New phase 3 study results on lumateperone, an adjunctive therapy to antidepressants. Psychiatric Times. April 16, 2024. https://www.psychiatrictimes.com/view/new-phase-3-study-results-on-lumateperone-an-adjunctive-therapy-to-antidepressants

4. O’Brien E. Evaluating the Efficacy of Lumateperone for MDD and Bipolar Depression With Mixed Features. Psychiatric Times. May 30, 2024. https://www.psychiatrictimes.com/view/evaluating-the-efficacy-of-lumateperone-for-mdd-and-bipolar-depression-with-mixed-features