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
Key facts
- 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
- Q3 2026 — Regulatory (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#
- mixedPhase 2 repeat-dose study topline: safety objective met for two-dose regimen; efficacy numerically separated from placebo but not statistically significant (exploratory)↗
- UpcomingFDA meeting on potential future Phase 3 registrational pathway for fasedienol in social anxiety disorder expected during Q3 2026↗
- missedPALISADE-4 Phase 3 topline: fasedienol missed primary and secondary endpoints in social anxiety disorder public speaking challenge↗
- Safety database milestone (ICH E1)Fasedienol SAD program exceeds ICH E1 minimum safety-exposure recommendations↗
- metPALISADE-3 open-label extension preliminary data: fasedienol well-tolerated over up to 12 months of as-needed use; clinically relevant improvement on LSAS and SPIN over four months↗
- 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.↗
- Workforce reduction / restructuringVistagen cuts ~20% of workforce to prioritize the fasedienol PALISADE program↗
- 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.
- Licensing dealVistagen out-licenses fasedienol (PH94B) to EverInsight (now AffaMed) for Greater China, South Korea and Southeast Asia↗
- Phase 2 proof-of-concept of PH94B in social anxiety disorder (NCT01217788, n=90) completed under originator/early development; supported subsequent development.
Clinical trials#
NCT06615557PALISADE-4Phase 3Activen=238
PALISADE-4: Fasedienol Nasal Spray for the Acute Treatment of Anxiety in Adults With Social Anxiety Disorder
United States
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
United States
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
United States
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
United States
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:
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)
- sec.gov — SEC filing
- 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: Positive Top-Line Results from Phase 3 PALISADE-2 Trial of Fasedienol in SAD (Aug 7, 2023) — U.S. SEC / Vistagen Therapeutics
Show all 18 sources
- Vistagen 8-K of 2026-03-05 (reduction in force) — Vistagen Therapeutics
- VistaGen Announces Completion of PALISADE-1 Phase 3 Clinical Study of PH94B (primary endpoint not met) — Vistagen Therapeutics (Business Wire)
- Vistagen Announces Preliminary Positive Data in Ongoing Open-Label Extension Portion of PALISADE-3 Phase 3 Study of Fasedienol for the Acute Treatment of Social Anxiety Disorder (8-K EX-99.1) — Vistagen Therapeutics
- Vistagen Announces Topline and Post-Hoc Data from PALISADE-4 Phase 3 Public Speaking Challenge Trial of Fasedienol for the Acute Treatment of Social Anxiety Disorder (8-K EX-99.1) — Vistagen Therapeutics
- Vistagen Announces Topline Results for Repeat Dose Study of Fasedienol for Acute Treatment of Social Anxiety Disorder (8-K EX-99.1) — Vistagen Therapeutics
- Vistagen ICH E1 safety-exposure milestone press release (8-K exhibit) — Vistagen Therapeutics
- Vistagen PALISADE-4 LPLV press release (8-K exhibit) — Vistagen Therapeutics
- VistaGen Therapeutics and EverInsight Therapeutics Enter Strategic Collaboration to Develop and Commercialize PH94B for Anxiety Disorders in Greater China, South Korea and Southeast Asia — PR Newswire / VistaGen Therapeutics, Inc.