The US Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for lumateperone (Caplyta) based on long-term data supporting the prevention of relapse in adults with schizophrenia.
Johnson & Johnson announced the lumateperone FDA approval on April 26, 2026. The approval stems from a phase 3 randomized withdrawal trial demonstrating a 63% reduction in relapse risk versus placebo over a 26-week double-blind treatment period.¹
"This label update, backed by long-term Phase 3 data demonstrating a significant delay in time to relapse, reinforces our commitment to advancing evidence-based therapies to support each patient's individual needs including a proven therapy supporting stability over time," said Celine Goldberger, MD, PhD, Vice President of Global Medical Affairs, Neuroscience, Innovative Medicine at Johnson & Johnson.
Lumateperone is already approved in adults for schizophrenia, as adjunctive therapy with antidepressants for major depressive disorder, and for depressive episodes associated with bipolar I or II disorder. The sNDA expands the label by incorporating long-term efficacy and tolerability data reinforcing its role in sustained disease management, an area of particular clinical interest given the frequency of relapse events in this population.
Lumateperone efficacy in the Study 304 randomized withdrawal trial
Study 304 was a multicenter, multinational, double-blind, placebo-controlled, randomized withdrawal study enrolling adults with schizophrenia.¹ The trial included an 18-week open-label phase during which patients received lumateperone 42 mg once daily. Patients meeting predefined stabilization criteria were randomized to continue lumateperone 42 mg (N=110) or switch to placebo (N=114) for up to 26 weeks.¹
On the primary endpoint, lumateperone significantly extended time to first symptom relapse compared with placebo during the double-blind phase (P = .0002).¹ Patients receiving lumateperone had a 63% lower risk of relapse versus placebo (hazard ratio, 0.37), and 84% of lumateperone-treated patients remained relapse-free over 6 months.¹ The key secondary endpoint, time to all-cause treatment discontinuation including relapse, also favored lumateperone, with a significant delay compared with placebo.¹
"These Phase 3 results, showing significantly longer time to relapse with 84% remaining relapse free over 6 months, provide clinicians with another tool offering long-term stability for people living with schizophrenia," said Christoph U. Correll, MD, clinical professor of psychiatry at the Zucker School of Medicine at Hofstra/Northwell, New York.
Lumateperone safety profile and metabolic outcomes in long-term use
The safety profile of lumateperone in Study 304 remained consistent with the existing body of clinical data, and no new safety concerns were identified, according to Johnson & Johnson.¹ The most common treatment-related adverse event was headache, occurring in at least 5% of patients and at least twice the rate observed with placebo.¹ No clinically relevant increases in prolactin or cardiometabolic parameters emerged at the end of the double-blind treatment period.¹
Data from a separate 12-month open-label extension study in schizophrenia further supported long-term tolerability. Patients treated with lumateperone experienced a mean weight change of −2.05 kg (−4.52 lbs) over one year, with sustained improvements or stability in metabolic parameters.¹ In prior short-term clinical studies, lumateperone was similar to placebo in weight change, metabolic effects, and extrapyramidal symptoms.¹
Lumateperone is also being evaluated in clinical studies for other neuropsychiatric and neurological conditions beyond its current FDA-approved indications, according to the company.¹
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