Small Molecule · RG7314

Balovaptan

DiscontinuedF. Hoffmann-La Roche Ltd (ROG)
  • FDA Breakthrough Therapy (Autism Spectrum Disorder; Granted 2018-01-29)

Oral, brain-penetrant, highly selective vasopressin V1a receptor (AVPR1A) antagonist discovered and developed by Roche (codes RG7314 / RO5285119), a triazolobenzodiazepine. Developed for the core social-communication difficulties of autism spectrum disorder: FDA Breakthrough Therapy Designation (2018-01-29) on the Phase 2 VANILLA adult study, but the Phase 3 V1aduct adult trial was stopped for futility (2020) and the Phase 2 aV1ation paediatric trial was negative, ending the ASD program. Roche then ran a small Phase 2 trial in PTSD (EXUVIA, NCT05401565, 2022-2023), which showed no meaningful difference from placebo, and dropped the PTSD asset in its full-year 2023 pipeline update. An IV formulation for prevention of malignant cerebral edema after acute ischemic stroke was planned but its Phase 2 was withdrawn before enrolment. No active development is known.

Also known as: RG7314, balovaptan, RO-5285119, RG-7314, RO5285119, 1228088-30-9, 8-chloro-5-methyl-1-(trans-4-(pyridin-2-yloxy)cyclohexyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

Data current as of

Key facts

Modality
Small molecule
Chemical class
triazolobenzodiazepine, pyridine
Chemistry
Achiral
Mechanism
V1A receptor antagonist
Highest phase
Discontinued
Lead indication
Autism spectrum disorder
Developer
F. Hoffmann-La Roche Ltd (ROG)
Designations
FDA Breakthrough Therapy (Autism Spectrum Disorder; Granted 2018-01-29)
Trials
6 tracked · 172 sites

Mechanism of action#

Selective, brain-penetrant antagonist of the arginine vasopressin V1a receptor (AVPR1A), a Gq-coupled class-A GPCR implicated in social behaviour. Human V1a Ki 0.7 nM ([3H]AVP displacement) and IC50 3 nM in a functional assay, with ~1,700-fold lower affinity at the V2 receptor (Ki 1,200 nM) and Kb-based selectivity ratios of ~2,700-3,900x over oxytocin and V2 receptors. The clinical hypothesis was that V1a blockade improves socialisation and communication in autism; it was later tested for PTSD symptom severity.

TargetActionAffinity
V1A receptorprimaryAVPR1AAntagonistKi 0.7 nMⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
Balovaptan oral 10 mg once daily
10 mg PO once daily in V1aduct (adult ASD Phase 3) and EXUVIA (PTSD Phase 2, 12 weeks); paediatric aV1ation used age-adjusted 4 mg and 10 mg adult-equivalent doses; VANILLA tested 1.5, 4 and 10 mg daily for 12 weeks.
OralOnce daily—

Development timeline#

201420162018202020222024Phase 211 Nov 2024 — readout (missed) — EXUVIA Phase 2 in adult PTSD: balovaptan 10 mg did not separate from placebo on CAPS-5 total severity at week 12 (-17.2 vs -15.6) or on any secondary endpoint.5 Oct 2023 — phase change — EXUVIA completed (actual primary completion and study completion 2023-10-05); 29 randomised.5 Oct 2023 — Trial (portion) completed — Phase 2 EXUVIA trial of balovaptan in PTSD completed2 Aug 2022 — phase change — EXUVIA Phase 2 in adult PTSD started (registry actual start 2022-08-02).29 Jan 2018 — Breakthrough Therapy — FDA grants Breakthrough Therapy Designation to balovaptan for autism spectrum disorder1 Sept 2013 — phase change — VANILLA Phase 2 in adult men with ASD started (registry start 2013-09).Phase 31 Aug 2022 — readout (missed) — aV1ation Phase 2 (339 children and adolescents 5-17 with ASD, 24 weeks): no difference vs placebo on Vineland-II 2DC (LS-mean difference -0.16; 90% CI -2.56 to 2.23; P=.91) or any secondary endpoint.10 Feb 2022 — readout (missed) — V1aduct Phase 3 (322 autistic adults, balovaptan 10 mg vs placebo, 24 weeks): terminated for futility; no improvement on Vineland-II 2DC (interim LS-mean change 2.91 vs 4.75 placebo; difference -1.84, 95% CI -5.15 to 1.48).1 Jul 2020 — Trial terminated — Phase 3 V1aduct trial of balovaptan in autistic adults terminated for futility30 Jun 2020 — Trial terminated — Paediatric Phase 2 aV1ation trial of balovaptan terminated8 May 2019 — readout (missed) — VANILLA Phase 2 (223 adult men with ASD, 12 weeks): no separation from placebo on the primary endpoint (SRS-2); dose-dependent improvements on the secondary Vineland-II composite at 4 mg and 10 mg.8 Aug 2018 — phase change — V1aduct Phase 3 in autistic adults started (registry start 2018-08-08; J Med Chem 2020 confirms phase 3 entry August 2018).
Phase change Readout Event UpcomingHover a marker for details.
Phase 2Sept 2013 – Nov 2024
  1. missedEXUVIA Phase 2 in adult PTSD: balovaptan 10 mg did not separate from placebo on CAPS-5 total severity at week 12 (-17.2 vs -15.6) or on any secondary endpoint.Post-traumatic stress disorder↗
  2. EXUVIA completed (actual primary completion and study completion 2023-10-05); 29 randomised.Post-traumatic stress disorder
  3. Trial (portion) completedPhase 2 EXUVIA trial of balovaptan in PTSD completedPost-traumatic stress disorder
  4. EXUVIA Phase 2 in adult PTSD started (registry actual start 2022-08-02).Post-traumatic stress disorder
  5. Breakthrough TherapyFDA grants Breakthrough Therapy Designation to balovaptan for autism spectrum disorderAutism spectrum disorder↗
  6. VANILLA Phase 2 in adult men with ASD started (registry start 2013-09).Autism spectrum disorder
Phase 3Aug 2018 – Aug 2022
  1. missedaV1ation Phase 2 (339 children and adolescents 5-17 with ASD, 24 weeks): no difference vs placebo on Vineland-II 2DC (LS-mean difference -0.16; 90% CI -2.56 to 2.23; P=.91) or any secondary endpoint.Autism spectrum disorder↗
  2. missedV1aduct Phase 3 (322 autistic adults, balovaptan 10 mg vs placebo, 24 weeks): terminated for futility; no improvement on Vineland-II 2DC (interim LS-mean change 2.91 vs 4.75 placebo; difference -1.84, 95% CI -5.15 to 1.48).Autism spectrum disorder↗
  3. Trial terminatedPhase 3 V1aduct trial of balovaptan in autistic adults terminated for futilityAutism spectrum disorder
  4. Trial terminatedPaediatric Phase 2 aV1ation trial of balovaptan terminatedAutism spectrum disorder
  5. missedVANILLA Phase 2 (223 adult men with ASD, 12 weeks): no separation from placebo on the primary endpoint (SRS-2); dose-dependent improvements on the secondary Vineland-II composite at 4 mg and 10 mg.Autism spectrum disorder↗
  6. V1aduct Phase 3 in autistic adults started (registry start 2018-08-08; J Med Chem 2020 confirms phase 3 entry August 2018).Autism spectrum disorder

Balovaptan for Autism spectrum disorder#

DiscontinuedDiscontinuedAutism spectrum disorder indication →

Balovaptan (RG7314), a selective oral vasopressin V1a antagonist, for the core socialisation and communication difficulties of autism spectrum disorder. The adult Phase 2 VANILLA study (NCT01793441, 223 men) missed its primary endpoint (SRS-2) but showed dose-dependent Vineland-II gains, earning FDA Breakthrough Therapy Designation on 2018-01-29. The Phase 3 V1aduct adult trial (NCT03504917, 322 participants, 10 mg daily, 24 weeks) was terminated for futility in 2020, and the paediatric Phase 2 aV1ation (NCT02901431, 339 children 5-17) showed no benefit.

Readouts

  • 2022-08-01ReportedFull resultsmissedNCT02901431

    aV1ation Phase 2 (339 children and adolescents 5-17 with ASD, 24 weeks): no difference vs placebo on Vineland-II 2DC (LS-mean difference -0.16; 90% CI -2.56 to 2.23; P=.91) or any secondary endpoint. ↗

  • 2022-02-10ReportedFull resultsmissedNCT03504917

    V1aduct Phase 3 (322 autistic adults, balovaptan 10 mg vs placebo, 24 weeks): terminated for futility; no improvement on Vineland-II 2DC (interim LS-mean change 2.91 vs 4.75 placebo; difference -1.84, 95% CI -5.15 to 1.48). ↗

  • 2019-05-08ReportedFull resultsmissedNCT01793441

    VANILLA Phase 2 (223 adult men with ASD, 12 weeks): no separation from placebo on the primary endpoint (SRS-2); dose-dependent improvements on the secondary Vineland-II composite at 4 mg and 10 mg. ↗

Balovaptan for Post-traumatic stress disorder#

DiscontinuedDiscontinuedPost-traumatic stress disorder indication →

EXUVIA (NCT05401565), a Phase 2 randomised, double-blind, placebo-controlled trial at eight US sites (Aug 2022 - Oct 2023), randomised 29 adults to balovaptan 10 mg daily or placebo for 12 weeks. No meaningful difference on the primary endpoint (CAPS-5 total change at week 12: -17.2 balovaptan vs -15.6 placebo) or any secondary endpoint; well tolerated.

Readouts

  • 2024-11-11ReportedFull resultsmissedNCT05401565

    EXUVIA Phase 2 in adult PTSD: balovaptan 10 mg did not separate from placebo on CAPS-5 total severity at week 12 (-17.2 vs -15.6) or on any secondary endpoint. ↗

Clinical trials#

NCT05401565BN43546Phase 2Completedn=29

Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With Post-Traumatic Stress Disorder (PTSD) (EXUVIA)

Started Aug 2022· Primary completion Oct 2023· 15 sites across 1 country

United States

NCT04049578WP40877Phase 1Discontinuedn=2

A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Balovaptan in Children With Autism Spectrum Disorder

Started Dec 2019· Primary completion Apr 2020· 5 sites across 1 country

United States

NCT03504917WN39434Phase 3Discontinuedn=322

A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension (V1aduct)

Started Aug 2018· Primary completion Mar 2020· 51 sites across 6 countries

United StatesItalyCanadaUnited Kingdom

NCT02901431BP30153Phase 2Discontinuedn=339

A Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Participants With Autism Spectrum Disorder (ASD) (aV1ation, paediatric)

Started Nov 2016· Primary completion Apr 2020· 45 sites across 1 country

United States

NCT01793441BP28420Phase 2Completedn=223

A Study of RG7314 to Investigate Efficacy and Safety in Individuals With Autism Spectrum Disorders (ASD) (VANILLA)

Started Sept 2013· Primary completion Sept 2016· 56 sites across 1 country

United States

Show all 6 trials

NCT03912350WP41045Phase 1Discontinued

The Effect of Hepatic Impairment on the Pharmacokinetics of Balovaptan (withdrawn, 0 enrolled)

Sources#

  1. Balovaptan, ChEMBL CHEMBL4297183 - bioactivities (human V1a Ki 0.7 nM; V2 Ki 1200 nM) — ChEMBL (EMBL-EBI)
  2. Bolognani F, et al. A phase 2 clinical trial of a vasopressin V1a receptor antagonist shows improved adaptive behaviors in men with autism spectrum disorder. Sci Transl Med. 2019;11(491):eaat7838 — Science Translational Medicine (AAAS) / PubMed
  3. Derks M, et al. Bioavailability and pharmacokinetic profile of balovaptan in healthy volunteers. Expert Opin Investig Drugs. 2021;30(8):893-901 — Expert Opinion on Investigational Drugs / PubMed
  4. FDA grants Breakthrough Therapy Designation for Roche's balovaptan in autism spectrum disorder (2018-01-29) — F. Hoffmann-La Roche Ltd
  5. Hollander E, et al. Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder (aV1ation). JAMA Psychiatry. 2022;79(8):760-769 — JAMA Psychiatry via PubMed Central
  6. Jacob S, et al. Efficacy and safety of balovaptan for socialisation and communication difficulties in autistic adults: a phase 3 randomised placebo-controlled trial (V1aduct). Lancet Psychiatry. 2022;9(3):199-210 — The Lancet Psychiatry / PubMed
  7. Marler S, et al. Efficacy and safety of balovaptan for posttraumatic stress disorder: A randomized, placebo-controlled trial. Exp Clin Psychopharmacol. 2025;33(1):43-52 — Experimental and Clinical Psychopharmacology (APA) / PubMed
  8. NCT01793441 - VANILLA Phase 2, adult ASD — ClinicalTrials.gov (U.S. National Library of Medicine)
  9. NCT02901431 - aV1ation Phase 2, paediatric ASD — ClinicalTrials.gov (U.S. National Library of Medicine)
  10. NCT03504917 - V1aduct Phase 3, adult ASD — ClinicalTrials.gov (U.S. National Library of Medicine)
Show all 13 sources
  1. NCT03912350 - Hepatic impairment PK study (withdrawn; cites ASD program stop) — ClinicalTrials.gov (U.S. National Library of Medicine)
  2. NCT04049578 - Phase 1 paediatric PK in ASD (terminated) — ClinicalTrials.gov (U.S. National Library of Medicine)
  3. NCT05401565 (BN43546) - Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With PTSD (results posted 2024-04-18) — ClinicalTrials.gov (U.S. National Library of Medicine)