Small Molecule · PH94B
Fasedienol (PH94B)
- Fast Track
Investigational, odorless, rapid-onset (~10-15 min) intranasal 'pherine' neuroactive steroid (3-beta-androsta-4,16-dien-3-ol) being developed by Vistagen for the acute, as-needed treatment of anxiety in adults with social anxiety disorder. Administered as a low-microgram nasal spray, fasedienol activates peripheral nasal chemosensory neurons whose signal is relayed via the olfactory bulb to limbic-amygdala fear/anxiety circuits and attenuates sympathetic autonomic tone, without systemic absorption, GABA-A potentiation, or direct activity on CNS neurons; it is locally metabolized in the nasal/olfactory mucosa. Originated at Pherin Pharmaceuticals; worldwide-licensed to Vistagen in 2018. FDA Fast Track designation (Dec 2019). Phase 3 PALISADE program: PALISADE-2 positive; PALISADE-1 and PALISADE-3 missed; PALISADE-4 topline anticipated 2Q 2026.
Also known as: PH94B, fasedienol, aloradine, 4-androstadienol, 3beta-androsta-4,16-dien-3-ol, 23062-06-8
- Modality
- Small molecule
- Chemical class
- neuroactive steroid, androstane
- Chemistry
- Single enantiomer
- Mechanism
- Nasal chemosensory receptor neurons agonist
- Highest phase
- Phase 3
- Lead indication
- Social anxiety disorder
- Developer
- Vistagen Therapeutics, Inc. (VTGN)
- Designations
- Fast Track
- Trials
- 4 tracked · 86 sites
- Next catalyst
- 2Q 2026 — Topline data (Social anxiety disorder)
Mechanism of action
Fasedienol is a synthetic neuroactive steroid 'pherine' that acts non-genomically and locally rather than via a conventional systemic receptor. After intranasal delivery it binds/activates receptors on peripheral nasal chemosensory neurons (olfactory/vomeronasal epithelium), which activate subsets of olfactory-bulb neurons connected to limbic-amygdala circuits implicated in fear and social anxiety, attenuating sympathetic autonomic tone within minutes. It is locally metabolized in the nasal mucosa with no measurable systemic absorption, no potentiation of GABA-A receptors, and no direct activity on neurons in the brain. Because the target is a peripheral chemosensory receptor system with no validated single cloned receptor and no measured binding constant, no clean Ki/IC50/affinity is citable (left null).
| Target | Action | Affinity |
|---|---|---|
| Nasal chemosensory receptor neuronsprimary | Agonist | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Fasedienol intranasal sprayaqueous metered nasal spray 3.2 μg per administration (delivered intranasally as a nasal spray, used as-needed prior to anxiety-provoking social situations) | Intranasal | As needed | — |
Development timeline
- PALISADE-4 (NCT06615557) completed last patient visit of the randomized portion; topline anticipated 2Q 2026 with a refined SAP (FDA had no comments). Program active.↗
- missedPALISADE-3 missed its primary SUDS endpoint (large placebo response); no secondary difference.↗
- Vistagen initiated the Phase 3 PALISADE program; PALISADE-1 (NCT04754802) first patient / study start.
- Phase 2 proof-of-concept of PH94B in social anxiety disorder (NCT01217788, n=90) completed under originator/early development; supported subsequent development.
Fasedienol (PH94B) for Social anxiety disorder
Phase 3ActiveSocial anxiety disorder indication →
Phase 3 PALISADE program for the acute, as-needed treatment of anxiety in adults with social anxiety disorder, using a single intranasal dose of fasedienol (3.2 ug) administered before a simulated public speaking challenge with Subjective Units of Distress Scale (SUDS) as the primary endpoint. PALISADE-1 (NCT04754802) missed its primary endpoint (2022); PALISADE-2 (NCT05011396) met its primary SUDS endpoint (p=0.015) and key secondary CGI-I endpoint (p=0.033) in Aug 2023 (described as the first positive US Phase 3 SAD study in over 15 years); PALISADE-3 (NCT06358651) missed its primary endpoint (reported Dec 17, 2025; both arms had a near-identical large response); PALISADE-4 (NCT06615557) completed its randomized portion (last patient visit May 2026) with topline results anticipated in 2Q 2026. Vistagen has stated PALISADE-4, if positive, together with PALISADE-2 could support a future US NDA; the program has FDA Fast Track designation (Dec 2019) and has met ICH E1 minimum safety-exposure recommendations (>1,500 subjects dosed as of May 31, 2026). Program remains active and undiscontinued as of June 2026.
Readouts
- 2Q 2026AnticipatedTopline dataNCT06615557
PALISADE-4 topline anticipated 2Q 2026; randomized portion complete. ↗
- 2025-12-17ReportedTopline datamissedNCT06358651
PALISADE-3 missed its primary SUDS endpoint (large placebo response); no secondary difference. ↗
- 2023-08-07ReportedTopline datametNCT05011396
PALISADE-2 met primary SUDS (p=0.015) and key secondary CGI-I (p=0.033) endpoints. ↗
- 2022-06-22ReportedTopline datamissedNCT04754802
PALISADE-1 missed its primary SUDS endpoint; tolerability favorable. ↗
Clinical trials
NCT06615557PALISADE-4Phase 3Activen=238
PALISADE-4: Fasedienol Nasal Spray for the Acute Treatment of Anxiety in Adults With Social Anxiety Disorder
pendingprimaryLS-mean change from baseline in SUDS score during public speaking challenge (single dose; SAP refined to include pre-IP SUDS as covariate)
Randomized portion completed (last patient visit May 8, 2026); topline results anticipated 2Q 2026 (not yet reported as of 2026-06-25). Open-label extension ongoing. SAP refined to incorporate each participant's pre-dose SUDS as a baseline covariate; FDA had no comments on the refinement.
NCT06358651PALISADE-3Phase 3Completedn=238
PALISADE-3: Fasedienol Nasal Spray for the Acute Treatment of Anxiety in Adults With Social Anxiety Disorder
missedprimaryLS-mean change from baseline in SUDS score during public speaking challenge — fasedienol 13.6 (+/-1.54 SE) vs placebo 14.0 (+/-1.51 SE); LS-mean difference ~0.4
PALISADE-3 did NOT achieve its primary endpoint: near-identical large SUDS reduction in both arms (fasedienol 13.6 +/-1.54 SE vs placebo 14.0 +/-1.51 SE); no treatment difference on secondary endpoints. Driven by an unexpectedly large placebo response. Safety favorable and consistent with prior trials. Per SEC 8-K (event date 2025-12-17).
NCT05011396PALISADE-2Phase 3Completedn=228
PALISADE-2: A US, Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Trial of PH94B (Fasedienol) Nasal Spray for the Acute Treatment of Anxiety Induced by a Public Speaking Challenge in Adult Subjects With Social Anxiety Disorder
metprimaryMean SUDS score change during public speaking challenge (Visit 2 baseline vs Visit 3 treatment) — LS-mean difference -5.8 (fasedienol -13.8 vs placebo -8.0) (0.015)
Met primary endpoint in the analysis population (n=141; fasedienol n=70, placebo n=71): statistically significant greater reduction in SUDS for fasedienol vs placebo (difference -5.8, p=0.015). Registry enrollment was 228; reported topline analysis population was 141.
metsecondaryProportion of clinician-assessed responders (CGI-I) — 37.7% fasedienol vs 21.4% placebo (0.033)
Met key secondary endpoint: significantly higher proportion of CGI-I responders ('much/very much less anxious') with fasedienol (37.7%) vs placebo (21.4%), p=0.033. Exploratory PGI-C responders 40.6% vs 18.6% (p=0.003).
NCT04754802PALISADE-1Phase 3Completedn=224
PALISADE-1: A US, Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Trial of PH94B (Fasedienol) Nasal Spray for the Acute Treatment of Anxiety Induced by a Public Speaking Challenge in Adult Subjects With Social Anxiety Disorder
missedprimaryMean SUDS score change during public speaking challenge (baseline vs treatment)
PALISADE-1 did not meet its primary SUDS endpoint vs placebo; results were inconsistent with prior positive Phase 2 data. Tolerability was favorable and consistent with other fasedienol trials.
Conference coverage
PH94B appears in 1 CNS Pulse conference abstract:
Identifiers
- ChEMBL CHEMBL5095042
- PubChem CID 9925482
- FDA UNII DTW1NJ7IJH
Sources
- Effect of fasedienol (PH94B) pherine nasal spray and steroidal hormones on electrogram responses and autonomic nervous system activity in healthy adult volunteers — Human Psychopharmacology: Clinical and Experimental (Wiley)
- PALISADE-1 Phase 3, PH94B/fasedienol in SAD (NCT04754802) — ClinicalTrials.gov
- PALISADE-2 Phase 3, PH94B/fasedienol in SAD (NCT05011396) — ClinicalTrials.gov
- PALISADE-3 Phase 3, fasedienol in SAD (NCT06358651) — ClinicalTrials.gov
- PALISADE-4 Phase 3, fasedienol in SAD (NCT06615557) — ClinicalTrials.gov
- Phase 2 study of PH94B in Social Anxiety Disorder (NCT01217788) — ClinicalTrials.gov
- Top-Line Results from Phase 3 PALISADE-2 Trial of Fasedienol (PH94B) Nasal Spray in Social Anxiety Disorder (SAD) — Cambridge University Press (CNS Spectrums)
- Vistagen 8-K (Item 8.01): PALISADE-3 Phase 3 did not achieve primary endpoint (event date Dec 17, 2025) — U.S. SEC / Vistagen Therapeutics
- Vistagen 8-K Exhibit 99.1: Completion of Last Patient Visit in PALISADE-4; topline expected 2Q 2026; Fast Track noted (May 8, 2026) — U.S. SEC / Vistagen Therapeutics
- Vistagen 8-K Exhibit 99.1: FY2026 results & corporate update; PALISADE-4 topline expected this month (June 15, 2026) — U.S. SEC / Vistagen Therapeutics
- Vistagen 8-K Exhibit 99.1: Positive Top-Line Results from Phase 3 PALISADE-2 Trial of Fasedienol in SAD (Aug 7, 2023) — U.S. SEC / Vistagen Therapeutics
- VistaGen Announces Completion of PALISADE-1 Phase 3 Clinical Study of PH94B (primary endpoint not met) — Vistagen Therapeutics (Business Wire)