Lumateperone Shows Promise in Preventing Schizophrenia Relapse

Key Insights

• Lumateperone 42 mg significantly extends the time to relapse in adults with schizophrenia, demonstrating a 63% reduction in relapse risk compared to placebo.
• A Phase 3 trial (Study 304) revealed that lumateperone also led to better treatment discontinuation rates during the double-blind phase, indicating improved tolerability.
• The drug was generally safe and well-tolerated, with headache being the most common adverse event reported at a rate greater than 5% and twice the rate of placebo.

Intra-Cellular Therapies has announced positive topline results from its Phase 3 Study 304, evaluating lumateperone (Caplyta) 42 mg for preventing relapse in adult patients with schizophrenia. The multi-center, multinational, randomized, double-blind, placebo-controlled trial demonstrated a significant delay in the time to first symptom relapse among patients treated with lumateperone compared to those receiving placebo.

The 47-week study included an 18-week open-label phase where patients with schizophrenia received lumateperone 42 mg daily. Those who met stabilization criteria then entered a double-blind treatment phase, randomized to either continue lumateperone 42 mg (N=114) or switch to placebo (N=114) for up to 26 weeks or until relapse.

Key Findings on Relapse Prevention

Lumateperone met the primary endpoint, showing a significantly longer time to relapse compared to placebo (P = 0.0002). Specifically, 16.4% of patients (18 individuals) in the lumateperone group experienced a relapse, compared to 38.6% (44 individuals) in the placebo group. This translates to a 63% reduction in the risk of relapse with lumateperone versus placebo (hazard ratio [95% CI] = 0.37, [0.22, 0.65]).

The study also met its secondary endpoint, demonstrating better treatment discontinuation rates during the double-blind phase (P = 0.0007).

Safety and Tolerability

Lumateperone was generally safe and well-tolerated. In the double-blind phase, the most commonly reported adverse event, occurring at a rate of ≥5% and twice the rate of placebo, was headache.

Broader Clinical Applications

Lumateperone is also being investigated for other psychiatric conditions. Earlier this year, Study 502 showed positive results for lumateperone 42 mg as an adjunctive therapy to antidepressants for major depressive disorder (MDD). The drug achieved statistically significant and clinically meaningful improvements in depressive symptoms, as measured by the Quick Inventory of Depressive Symptomatology Self Report (P < 0.0001).

Study 403 evaluated lumateperone 42 mg in adults aged 18-75 years with MDD or bipolar I or II disorder experiencing a major depressive episode with mixed features. Results indicated that lumateperone significantly improved symptoms compared to placebo, demonstrating efficacy and safety in this patient population.