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.
FREQUENTLY ASKED QUESTIONS:
What is lumateperone approved for?
Lumateperone (Caplyta) is FDA-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 as monotherapy or adjunctive therapy with lithium or valproate. The updated label now includes long-term data supporting relapse prevention in schizophrenia.
How does lumateperone work?
Lumateperone is characterized by antagonist activity at central serotonin 5-HT2A receptors and partial agonist activity at central dopamine D2 receptors, with high 5-HT2A occupancy and moderate D2 occupancy at therapeutic doses.
In a phase 3 randomized withdrawal trial, lumateperone 42 mg significantly extended time to relapse versus placebo over 26 weeks (P=.0002), reducing relapse risk by 63% (HR, 0.37), with 84% of patients remaining relapse-free at six months.
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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