ITI-007 · program

Lumateperone (ITI-007) for Major depressive disorder

ApprovedApprovedJohnson & Johnson (JNJ)

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

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

ApprovedMay 2005 – Nov 2025
  1. metFDA approved Caplyta (lumateperone) as adjunctive therapy with antidepressants for MDD in adults.↗
  2. Licensing dealIntra-Cellular in-licenses lumateperone (ITI-007) from Bristol-Myers Squibb↗
Filed (NDA)Dec 2024 – Apr 2025
  1. AcquisitionJohnson & Johnson acquires Intra-Cellular Therapies↗
  2. 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)

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.

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

Key secondary CGI-S endpoint met with statistical significance.

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. Johnson & Johnson Closes Landmark Intra-Cellular Therapies, Inc. Acquisition to Solidify Neuroscience Leadership — Johnson & Johnson
  7. Lumateperone (ligand 9099) - binding data at 5-HT2A, D2, and SERT — IUPHAR/BPS Guide to Pharmacology
  8. Lumateperone: First Approval — Drugs (Springer Nature)
  9. Study 501 (ITI-007-501): Lumateperone as adjunctive therapy in MDD (NCT04985942) — ClinicalTrials.gov
  10. Study 502 (ITI-007-502): Lumateperone as adjunctive therapy in MDD (NCT05061706) — ClinicalTrials.gov
  11. Study 503 (ITI-007-503): Open-label lumateperone as adjunctive therapy in MDD (NCT05061719) — ClinicalTrials.gov
  12. Study 505 (ITI-007-505): Lumateperone as adjunctive therapy in MDD (NCT05850689) — ClinicalTrials.gov