VHX-896 · program

Milsaperidone (VHX-896) for Major depressive disorder

Phase 3ActiveVanda Pharmaceuticals Inc. (VNDA)

Indications for VHX-896: Major depressive disorder · Phase 3 Bipolar disorder · Approved

Ongoing Phase 3 study of milsaperidone (Bysanti) as once-daily ADJUNCTIVE therapy in major depressive disorder (treatment-resistant MDD). Phase 3 study NCT06830044 (initiated Q4 2024, first listed start 3 Mar 2025; recruiting) evaluates milsaperidone vs placebo added to ongoing antidepressant therapy, primary endpoint MADRS change at 6 weeks. Vanda has stated results are expected in 2026 (the registry lists primary completion in March 2028 - see _comment). MDD is a development indication only: milsaperidone is FDA-approved (20 Feb 2026) for bipolar I and schizophrenia, NOT for MDD.

Data current as of

Development timeline

Phase 3Mar 2025 – Dec 2026
  1. UpcomingTopline data anticipated from the Phase 3 adjunctive MDD study of milsaperidone (Bysanti).↗
  2. On FDA approval of Bysanti for bipolar I and schizophrenia, Vanda restated that Bysanti remains in an ongoing Phase 3 study as a once-daily adjunctive treatment in treatment-resistant MDD, expected to complete by end of 2026. MDD remains investigational (Phase 3).↗
  3. Vanda (Q1 2025 results, SEC Form 8-K) confirmed the Bysanti Phase 3 once-daily adjunctive MDD study is ongoing with results expected in 2026; same filing reported the Bysanti NDA (bipolar I / schizophrenia, not MDD) accepted for filing with a 21 Feb 2026 PDUFA date.↗
  4. Phase 3 adjunctive MDD study NCT06830044 (milsaperidone vs placebo as add-on to ongoing antidepressant; primary MADRS at week 6; target n=500) initiated; program first announced by Vanda as initiated in Q4 2024 with results expected in 2026.

Readouts

  • 2026AnticipatedTopline dataNCT06830044

    Topline data anticipated from the Phase 3 adjunctive MDD study of milsaperidone (Bysanti). ↗

Clinical trials in Major depressive disorder

NCT06830044Phase 3Recruitingn=500

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

Started Mar 2025· Primary completion Mar 2028· 📍 38 sites across 4 countries (United States, Poland, Czechia, Bulgaria)

NCT04969211Phase 1Completedn=25

An Open-Label, Two-Period, Randomized, Single Oral Dose, Crossover Study to Evaluate the Bioequivalence of VHX-896 Tablets Relative to Iloperidone Tablets in Healthy Volunteers

Started Jun 2021· Primary completion Oct 2021

metprimarySingle-dose bioequivalence of VHX-896 vs iloperidone (Cmax, AUC)

Single-dose crossover study supporting that VHX-896 (milsaperidone) interconverts to iloperidone; plasma exposure parameters fell within standard regulatory bioequivalence limits relative to iloperidone. Supports the metabolite-bridging development strategy underlying all milsaperidone indications, including the adjunctive MDD program.

Formulations

FormulationRouteRegimenPharmacokinetics
Bysanti oral tablet
Immediate-release oral tablets, 1/2/4/6/8/10/12 mg; schizophrenia target 6-12 mg twice daily, bipolar I mania 12 mg twice daily
OralTwice dailyt½ 26 h · Tmax 4 h

Mechanism of action (compound-wide)

Atypical antipsychotic that, with its interconversion partner iloperidone, antagonizes dopamine D2, serotonin 5-HT2A and alpha1-adrenergic receptors; the metabolite shows highest affinity at 5-HT2A, with strong alpha1-adrenergic binding in excess of its dopamine D2 binding. Published receptor data are for the racemic P88-8991 metabolite (Subramanian & Kalkman 2002): pKi 5-HT2A 9.56 (~0.28 nM), alpha1-adrenergic 8.08 (~8.3 nM), D2A 7.80 (~16 nM); lower affinity at other dopamine, serotonin, alpha2-adrenergic and histamine H1 receptors. In MDD it is being studied as adjunctive (add-on) therapy to ongoing antidepressants, consistent with the atypical-antipsychotic adjunctive-depression mechanism.

TargetActionAffinity
5-HT2AprimaryHTR2AAntagonistKi 0.28 nMⓘ
alpha-1A adrenoceptorADRA1AAntagonistKi 8.3 nMⓘ
D2DRD2AntagonistKi 15.8 nMⓘ

← Full VHX-896 compound page (identity, identifiers, all indications)

Sources

  1. Bioequivalence study between VHX-896 and iloperidone tablets in healthy volunteers (NCT04969211) — ClinicalTrials.gov
  2. Bysanti (milsaperidone): Side Effects, Uses, Dosage, Interactions, Warnings (FDA prescribing information) — RxList / FDA label
  3. Phase 3 study of milsaperidone as adjunctive therapy in MDD (NCT06830044) — ClinicalTrials.gov
  4. Receptor profile of P88-8991 and P95-12113, metabolites of the novel antipsychotic iloperidone (Subramanian & Kalkman, Prog Neuropsychopharmacol Biol Psychiatry 2002;26(3):553-60) — Progress in Neuropsychopharmacology & Biological Psychiatry (PubMed)
  5. Vanda Pharmaceuticals Form 8-K (7 May 2025) - Q1 2025 results: Bysanti NDA accepted for filing (PDUFA 21 Feb 2026); Phase 3 adjunctive MDD study ongoing, results expected 2026 — U.S. SEC EDGAR / Vanda Pharmaceuticals Inc.
  6. Vanda Pharmaceuticals Form 8-K (filed 23 Feb 2026, dated 20 Feb 2026) - FDA approval of Bysanti (milsaperidone) for bipolar I and schizophrenia; ongoing Phase 3 adjunctive treatment-resistant MDD study expected to complete by end of 2026; D2/5-HT2A/alpha1 antagonism — U.S. SEC EDGAR / Vanda Pharmaceuticals Inc.