FDA Approves CAPLYTA sNDA for Schizophrenia Relapse Prevention

Key Takeaways

• The approval adds relapse prevention to the schizophrenia label in adults, as described by the company.
• During double-blind follow-up, continued lumateperone was associated with a lower relapse hazard than placebo, with a reported hazard ratio of 0.37.
• No new safety concerns were identified, the safety profile matched prior CAPLYTA data, and headache was the most common treatment-related adverse event.

The FDA approved a supplemental New Drug Application for CAPLYTA (lumateperone) for the prevention of relapse in schizophrenia after a pivotal phase 3 trial showed a 63% lower relapse risk with lumateperone than with placebo, according to Johnson & Johnson. The action expands the schizophrenia label in adults to include relapse-prevention language. Johnson & Johnson announced the decision in a sponsor-authored press release dated April 27, 2026. The update was based on long-term phase 3 data in adults with schizophrenia.

Support for the approval came from Study 304, a phase 3, multicenter, multinational, double-blind, placebo-controlled randomized withdrawal trial in adults with schizophrenia. The study began with an 18-week open-label phase in which participants received lumateperone 42 mg per day. Patients who met stabilization criteria then entered double-blind follow-up and were assigned to continue lumateperone 42 mg (N=110) or switch to placebo (N=114). This design focused the double-blind period on relapse prevention after stabilization.

In the 26-week double-blind period, CAPLYTA significantly extended time to relapse versus placebo, with p=0.0002, according to the company. The six-month relapse-free proportion was 84% among patients receiving lumateperone during follow-up. The relapse result was the primary endpoint, and all-cause discontinuation was the key secondary endpoint. The company also reported a significant delay in time to all-cause treatment discontinuation, including relapse, in the phase 3 randomized withdrawal study.

For safety, the company said no new concerns were identified and the profile was consistent with prior CAPLYTA data. Headache was the most common treatment-related adverse event and occurred in at least 5% of patients and at least twice the placebo rate. At the end of the double-blind period, no clinically relevant increases in prolactin or cardiometabolic parameters were reported.

In company product language, CAPLYTA 42 mg was described as an oral, once-daily atypical antipsychotic that does not require titration. The company linked that description to the updated schizophrenia relapse-prevention language rather than to a separate efficacy finding. It also cited a 12-month open-label extension in which mean weight change was -2.05 kg over one year, with sustained improvement or stability in metabolic parameters. Johnson & Johnson also said the update builds on existing clinical data and postmarketing experience across approved uses. Overall, the label update was based on long-term relapse-prevention and tolerability data in schizophrenia.