Phase 3 Data Shows Lumateperone Delays Schizophrenia Relapse Longer Than Placebo

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New phase 3 data showed that patients with schizophrenia on lumateperone (CAPLYTA) 42 mg had a significantly delayed relapse compared to patients on placebo.¹ Intra-Cellular Therapies announced the positive results of Study 304, a multicenter, multi-national, randomized, double-blind, placebo-controlled, parallel-group trial, on November 5, 2024.

Lumateperone (10.5 mg, 21 mg, 42 mg), an oral, once-daily atypical antipsychotic, is approved in adults for the treatment of schizophrenia and the treatment of depressive episodes linked to bipolar disorder as a monotherapy or an adjunctive therapy with lithium or valproate.^2,3 Lumateperone is believed to be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.

Research has indicated up to 81.9% of individuals with schizophrenia or schizoaffective disorder experience a relapse within 5 years of their diagnosis, with the global rate between 50 – 92%.^4,5 Subsequent relapses also have high rates.⁴ A schizophrenia relapse leads not only to increases in schizophrenia symptoms but to negative life impacts such as not adhering to medication, job or legal issues, self-harm, and hospitalization.

Study 304 evaluated the efficacy and safety of lumateperone 42 mg for the prevention of symptomatic relapse in adult patients with schizophrenia.¹ The 47-week trial started with an 18-week open-label phase where patients with schizophrenia were given lumateperone 42 mg per day. Participants who met the stabilization criteria during the open-label period continued to the double-blind treatment phase.

Participants were randomized to receive lumateperone 42 mg (n = 114) or placebo (n = 114) for up to 26 weeks or until a relapse. The primary endpoint was the time to the first symptom relapse, and the secondary endpoint was the time to all-cause discontinuation during the double-blind phase.

The study revealed the time to relapse during the double-blind treatment phase was significantly longer in patients receiving lumateperone compared with those receiving placebo (P = .0002). In total, 18 relapses (16.4%) occurred in the lumateperone group versus 44 relapses (38.6%) in the placebo group. Lumateperone was associated with a 63% reduction in risk of relapse compared with placebo (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22 – 0.65).

The data shows lumateperone is generally safe and well-tolerated. During the double-blind phase, participants commonly reported headaches, observed among ≥ 5% of the sample and twice the rate of placebo. Other common adverse events observed in previous clinical trials included somnolence/sedation, dizziness, nausea, and dry mouth.

“The control of symptoms and the prevention of relapses is critical to improving long-term patient outcomes,” said Suresh Durgam, MD, executive vice president and chief medical officer of Intra-Cellular Therapies. “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.”

References

1. ^{Intra-Cellular Therapies Announces Positive Topline Results in Phase 3 Trial Evaluating CAPLYTA for the Prevention of Relapse in Patients with Schizophrenia. Bio Space. November 5, 2024. https://www.biospace.com/press-releases/intra-cellular-therapies-announces-positive-topline-results-in-phase-3-trial-evaluating-caplyta-for-the-prevention-of-relapse-in-patients-with-schizophrenia. Accessed November 6, 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 November 6, 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 November 6, 2024.}
4. ^{Rivelli, A., Fitzpatrick, V., Nelson, M. et al. Real-world predictors of relapse in patients with schizophrenia and schizoaffective disorder in a large health system. Schizophr 10, 28 (2024). https://doi.org/10.1038/s41537-024-00448-2}
5. ^{Moges S, Belete T, Mekonen T, Menberu M. Lifetime relapse and its associated factors among people with schizophrenia spectrum disorders who are on follow up at Comprehensive Specialized Hospitals in Amhara region, Ethiopia: a cross-sectional study. Int J Ment Health Syst. 2021 May 6;15(1):42. doi: 10.1186/s13033-021-00464-0. PMID: 33957944; PMCID: PMC8101248.}