Small Molecule · Iloperidone LAI

Iloperidone LAI

Phase 3Vanda Pharmaceuticals Inc. (VNDA)

Long-acting injectable (intramuscular depot) formulation of iloperidone, an atypical antipsychotic (oral brand: Fanapt) developed by Vanda Pharmaceuticals. Iloperidone is a dopamine D2 / serotonin 5-HT2A antagonist with notably strong alpha-1 adrenergic antagonism; the active moiety is identical to the approved oral product, the depot only altering pharmacokinetics for sustained release. Oral iloperidone is FDA-approved (2009) for schizophrenia and (2024) for acute bipolar I; the LAI is in development to provide a long-acting maintenance/relapse-prevention option in schizophrenia. Originally researched by Hoechst Marion Roussel, licensed to Titan (1997) and Novartis (1998), and acquired by Vanda in 2004.

Also known as: Iloperidone LAI, VYV-683, iloperidone, Fanapt, 133454-47-4, 1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanone

Data current as of

Modality
Small molecule
Chemical class
benzisoxazole, Aryl ketone, piperidine
DEA schedule
Unscheduled
Chemistry
Achiral
Mechanism
5-HT2A antagonist
Highest phase
Phase 3
Lead indication
Schizophrenia
Developer
Vanda Pharmaceuticals Inc. (VNDA)
Trials
2 tracked · 1 recruiting · 25 sites
Next catalyst
Q4 2027 — Topline data (Schizophrenia)

Mechanism of action

Atypical antipsychotic that antagonizes dopamine D2 and serotonin 5-HT2A receptors, with distinctively strong alpha-1 adrenergic antagonism (which drives the dose-titration requirement to limit orthostatic hypotension). The long-acting injectable contains the same active moiety as oral iloperidone and does not alter receptor pharmacology; it is designed for sustained release to support maintenance treatment and relapse prevention. Reported human binding affinities: 5-HT2A Ki ~5.6 nM (Kongsamut et al., Eur J Pharmacol 1996), dopamine D2 Ki ~6.3 nM, alpha-1 adrenergic Ki ~0.36 nM.

TargetActionAffinity
5-HT2AprimaryHTR2AAntagonistKi 5.6 nMⓘ
alpha-1A adrenoceptorADRA1AAntagonistKi 0.36 nMⓘ
D2DRD2AntagonistKi 6.3 nMⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Iloperidone oral tablets (Fanapt)
Immediate-release oral tablets, titrated 1 mg BID to target 6-12 mg BID (12-24 mg/day)
OralTwice daily—
Iloperidone long-acting injectable (LAI)microsphere depot
Long-acting intramuscular depot injection in Phase 1/2 development for schizophrenia
Intramuscular——

Development timeline

Phase 3May 2025 – Nov 2027
  1. UpcomingAnticipated topline from the Phase 3 randomized-withdrawal relapse-prevention study of iloperidone LAI vs placebo in schizophrenia (primary endpoint: time to symptom exacerbation/relapse).
  2. Vanda's Q4/full-year 2025 financial results (PR 11 Feb 2026) confirmed the Phase 3 LAI iloperidone schizophrenia relapse-prevention study remains actively enrolling patients; no topline-data timing was guided.↗
  3. Pivotal Phase 3 randomized-withdrawal/relapse-prevention study of iloperidone LAI vs placebo injection in schizophrenia (NCT06961968; VP-VYV-683-3102; est. n=400; primary completion Nov 2027) started and began enrolling patients.
Phase 1Aug 2022
  1. Open-label, adaptive, repeat-dose Phase 1 study of iloperidone LAI safety/tolerability/PK in schizophrenia patients (NCT04712734, n=42) reached completion, establishing the depot formulation's pharmacokinetics ahead of the Phase 3 program.

Iloperidone LAI for Schizophrenia

Phase 3RecruitingSchizophrenia indication →

Vanda's long-acting injectable (LAI) formulation of iloperidone for schizophrenia maintenance / relapse prevention. The pivotal Phase 3 trial NCT06961968 (VP-VYV-683-3102) is a multicenter, double-blind, randomized-withdrawal study: after a 12-week open-label stabilization (oral iloperidone weeks 1-6, then iloperidone LAI weeks 7-12), stabilized patients are randomized 1:1 to continue iloperidone LAI or switch to placebo injection for up to 52 weeks, with the primary endpoint being time to exacerbation/relapse of psychiatric symptoms. The study began enrolling on 14 May 2025 (est. n=400; primary completion Nov 2027) and was confirmed 'enrolling patients' in Vanda's Q4/FY2025 results (Feb 2026). is_lead_indication=false because oral iloperidone (Fanapt) is already FDA-approved for schizophrenia; the LAI is a formulation line-extension. An earlier Phase 1 LAI PK/safety study (NCT04712734) completed in 2022.

Readouts

  • Q4 2027AnticipatedTopline dataNCT06961968

    Anticipated topline from the Phase 3 randomized-withdrawal relapse-prevention study of iloperidone LAI vs placebo in schizophrenia (primary endpoint: time to symptom exacerbation/relapse).

Clinical trials

NCT06961968VP-VYV-683-3102Phase 3Recruitingn=400

A Multicenter, Double-Blind, Randomized Withdrawal Study in Patients With Schizophrenia Receiving Either Iloperidone Long-Acting Injection (LAI) or Placebo Injection

Started May 2025· Primary completion Nov 2027· 📍 22 sites across 1 country (United States)

NCT04712734Phase 1Completedn=42

An Open-label, Adaptive, Repeat-dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Iloperidone Long-acting Injection (LAI) in Patients With Schizophrenia

Started Jan 2021· Primary completion Aug 2022· 📍 3 sites across 1 country (United States)

Related compounds

Other 5-HT2A compounds

More from Vanda Pharmaceuticals Inc.

Identifiers

Sources

  1. A Multicenter, Double-Blind, Randomized Withdrawal Study in Patients With Schizophrenia Receiving Either Iloperidone LAI or Placebo Injection (NCT06961968; Vanda; Phase 3; internal code VP-VYV-683-3102; recruiting; n=400; primary completion Nov 2027) — ClinicalTrials.gov
  2. An Open-label, Adaptive, Repeat-dose Study to Evaluate Safety, Tolerability and PK of Iloperidone LAI in Schizophrenia (NCT04712734; Vanda; Phase 1; completed 2022-08-30; n=42) — ClinicalTrials.gov
  3. FANAPT (iloperidone) tablets - Prescribing Information — FDA (Drugs@FDA)
  4. Iloperidone - pharmacology / receptor binding table (consensus human Ki: D2 6.3 nM, 5-HT2A 5.6 nM, alpha-1 0.36 nM; cites Mauri et al. 2014 EXCLI J) and development history (Hoechst Marion Roussel -> Titan -> Novartis -> Vanda) — Wikipedia
  5. Iloperidone binding to human and rat dopamine and 5-HT receptors (Kongsamut et al., Eur J Pharmacol 1996;317(2-3):417-423) - human 5-HT2A Ki 5.6 nM, D3 7.1, D4 25, 5-HT2C 42.8 nM — European Journal of Pharmacology (PubMed)
  6. Vanda Announces U.S. Patent Allowance for a Long-Acting Injectable Formulation of Fanapt (iloperidone) — Vanda Pharmaceuticals / PR Newswire
  7. Vanda Pharmaceuticals Reports Fourth Quarter and Full Year 2025 Financial Results — Vanda Pharmaceuticals Inc. / PR Newswire