ITI-007 · program

Lumateperone (ITI-007) for Major depressive disorder

ApprovedApprovedJohnson & Johnson (JNJ)

Indications for ITI-007: Schizophrenia · Approved Bipolar depression · Approved Bipolar disorder · Phase 3 Autism spectrum disorder · Phase 3 Major depressive disorder · Approved

FDA approved Caplyta (lumateperone) 42 mg once daily on 6 Nov 2025 as adjunctive therapy with antidepressants for major depressive disorder in adults. Approval (an sNDA, submitted 3 Dec 2024) was supported by two positive pivotal Phase 3 trials, Study 501 (NCT04985942) and Study 502 (NCT05061706), each showing a statistically significant MADRS separation from placebo at Week 6 (-4.9 / ES 0.61 and -4.5 / ES 0.56, both p<0.0001) plus a significant CGI-S key secondary, with a 6-month open-label extension (Study 503, NCT05061719) showing 80% response / 65% remission. This is MDD-specific; the compound was already approved for schizophrenia and for bipolar I/II depression. Originated by Intra-Cellular Therapies, which J&J acquired (closed 2 Apr 2025); Caplyta is now marketed by Johnson & Johnson Innovative Medicine. is_lead_indication=false because schizophrenia was the original (lead) approved indication.

Data current as of

Development timeline

ApprovedNov 2025
  1. metFDA approved Caplyta (lumateperone) as adjunctive therapy with antidepressants for MDD in adults.↗
Filed (NDA)Dec 2024
  1. Intra-Cellular Therapies submitted the sNDA to FDA for Caplyta (lumateperone) as adjunctive therapy for MDD, based on Studies 501 and 502.↗
Phase 3Apr 2024 – Jun 2024
  1. metStudy 502 positive: lumateperone + antidepressant met MADRS primary (-4.5 vs placebo, p<0.0001) and CGI-S key secondary at Week 6.↗
  2. metStudy 501 positive: lumateperone + antidepressant met MADRS primary (-4.9 vs placebo, p<0.0001) and CGI-S key secondary at Week 6.↗

Readouts

  • 2025-11-06ReportedRegulatorymet

    FDA approved Caplyta (lumateperone) as adjunctive therapy with antidepressants for MDD in adults. ↗

  • 2024-06-18ReportedTopline datametNCT05061706

    Study 502 positive: lumateperone + antidepressant met MADRS primary (-4.5 vs placebo, p<0.0001) and CGI-S key secondary at Week 6. ↗

  • 2024-04-16ReportedTopline datametNCT04985942

    Study 501 positive: lumateperone + antidepressant met MADRS primary (-4.9 vs placebo, p<0.0001) and CGI-S key secondary at Week 6. ↗

Clinical trials in Major depressive disorder

NCT05850689ITI-007-505Phase 3Recruitingn=470

Study 505: A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Started May 2023· Primary completion Sept 2026· 📍 60 sites across 7 countries (United States, India, Bulgaria, Serbia)

NCT05061706ITI-007-502Phase 3Completedn=480

Study 502: A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Started Sept 2021· Primary completion Apr 2024· 📍 50 sites across 7 countries (United States, Poland, Argentina, Germany)

metsecondaryCGI-S (severity) change from baseline at Week 6 — ES 0.51 (<0.0001)

Key secondary CGI-S endpoint met with statistical significance.

metprimaryMADRS total score change from baseline to Day 43 (Week 6), lumateperone 42 mg + ADT vs placebo + ADT — LSMD -4.5; ES 0.56 (<0.0001)

Primary MADRS endpoint met: statistically significant, clinically meaningful separation from placebo at Week 6. n=480, 1:1. Second pivotal study.

NCT04985942ITI-007-501Phase 3Completedn=485

Study 501: A Randomized, Double-Blind, Placebo-controlled Multicenter Study to Assess the Efficacy and Safety of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

Started Jul 2021· Primary completion Feb 2024· 📍 54 sites across 6 countries (India, United States, Bulgaria, Slovakia)

metsecondaryCGI-S (severity) change from baseline at Week 6 — ES 0.67 (<0.0001)

Key secondary CGI-S endpoint met with statistical significance.

metprimaryMADRS total score change from baseline to Day 43 (Week 6), lumateperone 42 mg + ADT vs placebo + ADT — LSMD -4.9 (lumateperone -14.7 vs placebo -9.8); ES 0.61 (<0.0001)

Primary MADRS endpoint met: statistically significant, clinically meaningful separation from placebo at Week 6 in patients with inadequate antidepressant response. n=485, 1:1.

NCT05061719ITI-007-503Phase 3Completed

Study 503: An Open-label Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder

· 📍 109 sites across 11 countries (United States, Bulgaria, Poland, India)

metsecondaryLong-term response and remission over 26 weeks (open-label extension) — 80% response; 65% remission (MADRS total <=10) at 6 months

6-month open-label safety/extension study: 80% of patients responded and 65% achieved remission at 6 months; supported the long-term safety/efficacy package for the MDD sNDA.

Formulations

FormulationRouteRegimenPharmacokinetics
Lumateperone oral capsule (Caplyta)immediate-release capsule (crystalline tosylate salt)
Capsules of 42 mg, 21 mg, and 10.5 mg lumateperone (equivalent to 60/30/15 mg lumateperone tosylate); recommended dose 42 mg once daily, with or without food.
OralOnce dailyt½ 18 h · Tmax 1.5 h · F 4.4%

Mechanism of action (compound-wide)

Multi-target small molecule. High-affinity serotonin 5-HT2A receptor antagonist (human pKi 9.3, Ki ~0.50 nM) with comparatively lower affinity at dopamine D2 receptors (pKi 7.5, Ki ~32 nM) where it acts as a presynaptic partial agonist / postsynaptic antagonist (the developer's 'dopamine receptor phosphoprotein modulator' framing), and inhibition of the serotonin transporter (SERT; pKi 7.2, Ki ~63 nM). Also modulates dopamine D1-receptor-dependent glutamatergic signaling. The combined 5-HT2A antagonism plus low/region-selective D2 occupancy and SERT inhibition underlies its low metabolic/EPS burden and proposed antidepressant activity.

TargetActionAffinity
5-HT2AprimaryHTR2AAntagonistKi 0.5 nMⓘ
D2DRD2AntagonistKi 32 nMⓘ
SERTSLC6A4InhibitorKi 63 nMⓘ

← Full ITI-007 compound page (identity, identifiers, all indications)

Sources

  1. CAPLYTA (lumateperone) capsules - Prescribing Information — DailyMed / NIH (FDA label)
  2. FDA approval of Caplyta (lumateperone) for adjunctive MDD in adults — Johnson & Johnson (PR Newswire)
  3. Intra-Cellular Therapies announces positive Phase 3 topline results from Study 501 (adjunctive MDD) — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  4. Intra-Cellular Therapies announces positive topline results in second Phase 3 trial (Study 502, adjunctive MDD) — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  5. Intra-Cellular Therapies submits sNDA to FDA for Caplyta (lumateperone) for adjunctive MDD — Intra-Cellular Therapies, Inc. (GlobeNewswire)
  6. Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology
  7. Study 501 (ITI-007-501): Lumateperone as adjunctive therapy in MDD (NCT04985942) — ClinicalTrials.gov
  8. Study 502 (ITI-007-502): Lumateperone as adjunctive therapy in MDD (NCT05061706) — ClinicalTrials.gov
  9. Study 503 (ITI-007-503): Open-label lumateperone as adjunctive therapy in MDD (NCT05061719) — ClinicalTrials.gov
  10. Study 505 (ITI-007-505): Lumateperone as adjunctive therapy in MDD (NCT05850689) — ClinicalTrials.gov