Sepranolone · program

Sepranolone for Tourette syndrome

Phase 2CompletedRelmada Therapeutics, Inc. (RLMD)

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.

Data current as of

Development timeline

Phase 2Feb 2023 – Feb 2025
  1. 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.↗
  2. 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.↗
  3. Phase 2a Tourette study NCT05434546 reached primary completion (actual). Results published by Asarina Pharma 2023-04-01.

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 in Tourette syndrome

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)

Started Feb 2022· Primary completion Feb 2023· 📍 2 sites across 1 country (Denmark)

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.

Formulations

FormulationRouteRegimenPharmacokinetics
Sepranolone subcutaneous injection (Tourette syndrome)
10 mg by subcutaneous injection twice weekly (Phase 2a, in addition to standard of care)
SubcutaneousTwice weekly—

Mechanism of action (compound-wide)

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.

TargetActionAffinity
GABA-A receptorprimaryAntagonist—ⓘ

← Full Sepranolone compound page (identity, identifiers, all indications)

Sources

  1. A Study to Explore the Effect of Sepranolone in Tourette Syndrome (NCT05434546) — ClinicalTrials.gov
  2. Asarina Pharma publishes positive results from its Phase IIa study of Sepranolone in Tourette Syndrome — Asarina Pharma AB (via Nasdaq)
  3. Positive GABAA receptor modulating steroids and their antagonists: Implications for clinical treatments (Backstrom et al., 2022) — Journal of Neuroendocrinology (Wiley)
  4. Relmada Therapeutics Acquires Potential Therapy for Tourette Syndrome from Asarina Pharma AB — Relmada Therapeutics, Inc.
  5. Relmada Therapeutics Acquires Potential Therapy for Tourette Syndrome from Asarina Pharma AB — Relmada Therapeutics, Inc.