Neuroactive Steroid · Sepranolone
Sepranolone
Sepranolone (isoallopregnanolone; UC1010; INN sepranolone) is an endogenous neuroactive steroid, the 3-beta epimer of allopregnanolone. It is a first-in-class GABA-A Modulating Steroid Antagonist (GAMSA) that selectively antagonizes allopregnanolone's positive allosteric modulation of the GABA-A receptor without affecting GABA-A signaling per se. Originated and developed by Asarina Pharma AB; global rights acquired by Relmada Therapeutics in February 2025 (Phase 2b-ready for Tourette syndrome and other compulsion-related conditions).
Also known as: Sepranolone, Isoallopregnanolone, Isopregnanolone, UC1010, UC-1010, 3beta-hydroxy-5alpha-pregnan-20-one, 516-55-2
- Modality
- Neuroactive Steroid
- Chemical class
- neuroactive steroid, pregnane steroid
- Chemistry
- Single enantiomer
- Mechanism
- GABA-A receptor antagonist
- Highest phase
- Phase 2
- Lead indication
- Tourette syndrome
- Developer
- Relmada Therapeutics, Inc. (RLMD)
- Trials
- 1 tracked · 2 sites
Mechanism of action
Sepranolone is a GABA-A Modulating Steroid Antagonist (GAMSA): it selectively antagonizes the positive allosteric modulation of the GABA-A receptor produced by the neurosteroid allopregnanolone (ALLO), without acting on the GABA-A receptor itself and without antagonizing GABA, benzodiazepines, or barbiturates. In Tourette syndrome, stress-induced ALLO is hypothesized to enhance tics; sepranolone is proposed to counteract this ALLO-mediated GABA-A modulation.
| Target | Action | Affinity |
|---|---|---|
| GABA-A receptorprimary | Antagonist | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| Sepranolone (UC1010) subcutaneous injection (PMDD) 10 or 16 mg by subcutaneous injection every second day during the luteal phase | Subcutaneous | — | — |
| Sepranolone subcutaneous injection (Tourette syndrome) 10 mg by subcutaneous injection twice weekly (Phase 2a, in addition to standard of care) | Subcutaneous | Twice weekly | — |
Development timeline
- Relmada Therapeutics acquired full global rights to sepranolone from Asarina Pharma (EUR 3M asset purchase); described as Phase 2b-ready for Tourette syndrome and other compulsion-related conditions.↗
- mixedSepranolone Phase 2a in Tourette syndrome: 28% YGTSS tic reduction vs 12.6% control (p=0.051); all secondary endpoints (PUTS, GTS-QOL, impairment) favored sepranolone; favorable safety.↗
- Phase 2a Tourette study NCT05434546 reached primary completion (actual). Results published by Asarina Pharma 2023-04-01.
Sepranolone for Tourette syndrome
Phase 2CompletedTourette syndrome indication →
Phase 2a, randomized, open-label, multicenter exploratory study (NCT05434546) of subcutaneous sepranolone added to standard of care in patients aged 12-55 with Tourette syndrome. Completed February 2023 with a numerically positive primary YGTSS effect (p=0.051) and consistent secondary-endpoint benefits. Asset acquired by Relmada (Feb 2025) and described as Phase 2b-ready; no active Phase 2b trial registered as of the cutoff.
Readouts
- 2023-04-01ReportedTopline datamixedNCT05434546
Sepranolone Phase 2a in Tourette syndrome: 28% YGTSS tic reduction vs 12.6% control (p=0.051); all secondary endpoints (PUTS, GTS-QOL, impairment) favored sepranolone; favorable safety. ↗
Clinical trials
NCT05434546APH205Phase 2Completedn=26
A Randomized, Open-label, Multicenter, Phase 2 Clinical Trial to Explore the Safety and Efficacy of Sepranolone in Pediatric and Adult Patients With Tourette Syndrome (sponsor of record: Asarina Pharma)
mixedprimaryChange from baseline in Yale Global Tic Severity Scale (YGTSS) total tic score at week 12 — Sepranolone -8.6 points (-28.0%) vs control -3.9 points (-12.6%) (0.051)
Sepranolone (10 mg SC twice weekly x 12 weeks + standard of care, n=17 active) reduced YGTSS total tic score by 8.6 points (28.0%) vs 3.9 points (12.6%) in the standard-of-care control arm (n=9); between-group p=0.051 (did not reach p<0.05). Captured as 'mixed': primary numerically favored sepranolone but narrowly missed significance.
metsecondaryYGTSS impairment scale — Moderate-to-marked impairment fell from 50% to 19% (sepranolone) vs unchanged 50% (control)
On the YGTSS impairment subscale, the proportion of sepranolone patients with moderate-to-marked symptoms fell from 50% to 19%, while the control group was unchanged at 50%.
metsecondaryTourette-specific quality of life (GTS-QOL) — 69% greater quality-of-life improvement in sepranolone vs control
GTS-QOL showed a 69% greater increase in quality of life for the sepranolone group versus the control group.
metsecondaryPremonitory Urge for Tics Scale (PUTS) reduction — 44% greater reduction in sepranolone vs control
Premonitory urge to tic (PUTS) showed a 44% greater reduction in the sepranolone group than in the control group.
Identifiers
- ChEMBL CHEMBL2057301
- PubChem CID 92787
- FDA UNII 3P8Z6V53MU
Sources
- A Study to Explore the Effect of Sepranolone in Tourette Syndrome (NCT05434546) — ClinicalTrials.gov
- Asarina Pharma publishes positive results from its Phase IIa study of Sepranolone in Tourette Syndrome — Asarina Pharma AB (via Nasdaq)
- Positive GABAA receptor modulating steroids and their antagonists: Implications for clinical treatments (Backstrom et al., 2022) — Journal of Neuroendocrinology (Wiley)
- Relmada Therapeutics Acquires Potential Therapy for Tourette Syndrome from Asarina Pharma AB — Relmada Therapeutics, Inc.
- Relmada Therapeutics Acquires Potential Therapy for Tourette Syndrome from Asarina Pharma AB — Relmada Therapeutics, Inc.
- Treatment of premenstrual dysphoric disorder with the GABAA receptor modulating steroid antagonist Sepranolone (UC1010) - A randomized controlled trial — PubMed (Psychoneuroendocrinology)