FDA Approves Caplyta as Adjunctive Remedy for Main Depressive Dysfunction Based mostly on Constructive Part III Outcomes

The FDA has accepted Caplyta (lumateperone) as an adjunctive remedy with antidepressants for the therapy of main depressive dysfunction (MDD) in adults, marking the remedy’s fourth indication.¹

Caplyta’s most up-to-date FDA approval relies on constructive outcomes from two Part III scientific trials: Examine 501 (NCT04985942) and Examine 502 (NCT05061706). Each research met their main endpoint and key secondary measures, demonstrating a big enchancment in melancholy signs.

Approval primarily based on constructive outcomes throughout Part III program

Examine 501 and Examine 502 are each international, double-blind, placebo-controlled trials. Their affected person populations had been comprised of these with a main analysis of MDD who additionally had an insufficient response to ongoing antidepressant remedy.

Outcomes throughout each trials confirmed:

• Caplyta added to an antidepressant achieved important enchancment in Montgomery-Asberg Despair Score Scale (MADRS) complete rating versus placebo, with separations of 4.9 and 4.5 factors (impact sizes 0.61 and 0.56).
• Caplyta demonstrated a positive security and tolerability profile, together with minimal metabolic, weight, and movement-related results.
• The commonest adversarial occasions (≥5% and ≥2× placebo) had been dizziness, dry mouth, somnolence/sedation, nausea, fatigue, and diarrhea.
• Metabolic and weight modifications had been akin to placebo, and charges of extrapyramidal signs had been low.

In a press launch, Roger S. McIntyre, MD, FRCPC, professor of psychiatry and pharmacology, College of Toronto, stated: “Despair is a posh dysfunction that impacts every particular person in another way, underscoring the pressing want for a spread of efficient and well-tolerated therapy choices. “For people who find themselves nonetheless experiencing lingering depressive signs whereas on an antidepressant, including Caplyta to a affected person’s therapy routine could supply early enchancment, with the potential for remission—the final word objective of therapy.”

Lengthy-term information reinforce Caplyta’s efficacy

Caplyta was additionally evaluated in Examine 503 (NCT05061719), an open-label extension security trial. Information from the 26-week examine confirmed that 80% of sufferers responded to therapy and 65% of sufferers skilled remission at six months.

• Examine 503 evaluated the long-term security of adjunctive Caplyta 42 mg in sufferers who accomplished Research 501 or 502.
• The first endpoint assessed security and tolerability, together with adversarial occasions, extrapyramidal signs, suicidality, and modifications in labs, vitals, and electrocardiogram measures.
• The secondary endpoint evaluated enchancment or upkeep of depressive signs through modifications in MADRS complete and Medical International Impression Scale-Severity index (CGI-S) scores from baseline to week 26.

In July, Johnson & Johnson submitted a supplemental New Drug Software (sNDA) to the FDA with long-term information for Caplyta within the prevention of relapse in schizophrenia. Analysis in different neuropsychiatric and neurological issues is ongoing.

Earlier FDA approval for bipolar dysfunction

Caplyta was accepted by the FDA in December 2021 for the therapy of depressive episodes related to bipolar I or II dysfunction in adults, as monotherapy and as adjunctive remedy with lithium or valproate.²

This earlier approval was primarily based on information from two Part III research: Examine 404 (NCT03249376) which evaluated Caplyta as monotherapy, and Examine 402 (NCT02600507) which evaluated Caplyta alongside lithium or valproate.

Information from each trials confirmed:

• Caplyta 42 mg achieved statistically important enhancements over placebo in MADRS complete rating change at week 6.
• The drug additionally demonstrated a statistically important enchancment in the important thing secondary endpoint measuring scientific international impression of bipolar dysfunction.
• Caplyta® demonstrated a positive security and tolerability profile according to prior schizophrenia research.
• The commonest adversarial reactions (≥5% and ≥2× placebo) had been somnolence/sedation, dizziness, nausea, and dry mouth.
• Imply modifications in weight, fasting glucose, ldl cholesterol, triglycerides, and LDL ranges had been akin to placebo.

References

1. FDA approval of CAPLYTA® (lumateperone) has the potential to reset therapy expectations, providing hope for remission in adults with main depressive dysfunction. Information launch. Johnson & Johnson. November 6, 2025. Accessed November 7, 2025. https://www.jnj.com/media-center/press-releases/fda-approval-of-caplyta-lumateperone-has-the-potential-to-reset-treatment-expectations-offering-hope-for-remission-in-adults-with-major-depressive-disorder

2. Intra-Mobile Therapies Proclaims U.S. FDA Approval of CAPLYTA® (lumateperone) for the Remedy of Bipolar Despair in Adults. Information launch. Intra-Mobile Therapies. December 20, 2021. Accessed November 7, 2025. https://www.globenewswire.com/news-release/2021/12/20/2355071/0/en/Intra-Mobile-Therapies-Proclaims-U-S-FDA-Approval-of-CAPLYTA-lumateperone-for-the-Remedy-of-Bipolar-Despair-in-Adults.html