RG7314 · program

Balovaptan for Autism spectrum disorder

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

Indications for RG7314: Autism spectrum disorder · Discontinued Post-traumatic stress disorder · Discontinued

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.

Data current as of

Development timeline

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.↗
  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).↗
  3. Trial terminatedPhase 3 V1aduct trial of balovaptan in autistic adults terminated for futility
  4. Trial terminatedPaediatric Phase 2 aV1ation trial of balovaptan terminated
  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.↗
  6. V1aduct Phase 3 in autistic adults started (registry start 2018-08-08; J Med Chem 2020 confirms phase 3 entry August 2018).
Phase 2Sept 2013 – Jan 2018
  1. Breakthrough TherapyFDA grants Breakthrough Therapy Designation to balovaptan for autism spectrum disorder↗
  2. VANILLA Phase 2 in adult men with ASD started (registry start 2013-09).

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. ↗

Clinical trials in Autism spectrum disorder

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 States, Italy, Canada, United 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)

NCT03912350WP41045Phase 1Discontinued

The Effect of Hepatic Impairment on the Pharmacokinetics of Balovaptan (withdrawn, 0 enrolled)

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—

Mechanism of action (compound-wide)

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ⓘ

← Full RG7314 compound page (identity, identifiers, all indications)

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. NCT01793441 - VANILLA Phase 2, adult ASD — ClinicalTrials.gov (U.S. National Library of Medicine)
  8. NCT02901431 - aV1ation Phase 2, paediatric ASD — ClinicalTrials.gov (U.S. National Library of Medicine)
  9. NCT03504917 - V1aduct Phase 3, adult ASD — ClinicalTrials.gov (U.S. National Library of Medicine)
  10. NCT03912350 - Hepatic impairment PK study (withdrawn; cites ASD program stop) — ClinicalTrials.gov (U.S. National Library of Medicine)
  11. NCT04049578 - Phase 1 paediatric PK in ASD (terminated) — ClinicalTrials.gov (U.S. National Library of Medicine)