balovaptan (RG7314) / Roche - LARVOL DELTA

Predictors of Placebo Response in the Study of Oxytocin in Autism to Improve Reciprocal Social Behaviors. (PubMed, J Child Adolesc Psychopharmacol) - "This is consistent with the finding that lower social communication adaptive functioning was associated with greater placebo response in recent RCTs of balovaptan for social impairment in autism. However, it contrasts with findings from a trial of citalopram for repetitive behavior in autism, in which lower baseline severity of a composite of autistic and mood symptoms predicted greater placebo response. This may indicate that different factors contribute to placebo response in different symptom domains."

Clinical • Journal • Autism Spectrum Disorder • Genetic Disorders

Efficacy and safety of balovaptan for posttraumatic stress disorder: A randomized, placebo-controlled trial. (PubMed, Exp Clin Psychopharmacol) - P2 | "Balovaptan was well tolerated with no new safety findings. The number of participants with at least one adverse event of any intensity was 9/13 (69.2%) in the balovaptan group and 7/16 (43.8%) in the placebo group."

Journal • CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

The pediatric psychopharmacology of autism spectrum disorder: A systematic review part II: The future. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "RCTs of drugs with the strongest foundation in preclinical research, namely arbaclofen, balovaptan and bumetanide have all failed to reach their primary end-points, although efforts to target specific patient subgroups do warrant further investigation...However, a small subset of compounds, including N-acetylcysteine, folinic acid, l-carnitine, coenzyme Q10, sulforaphane, and metformin may already be considered, with due caution, for clinical use, because there is promising evidence of efficacy and a high safety profile. For several other compounds, such as secretin, efficacy can be confidently excluded, and/or the data discourage undertaking new RCTs. Part I and Part II summarize "drug-based" information, which will be ultimately merged to provide clinicians with a "symptom-based" consensus statement in a conclusive Part III, with the overarching aim to foster evidence-based clinical practices and to organize new strategies for future clinical trials."

Journal • Review • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Pediatrics • Psychiatry

Radiolabeling and imaging of a novel 18F-labeled probe targeting the arginine vasopressin receptor V1a (SNMMI 2024) - " Based on the structure-activity analysis of the V1a antagonist balovaptan developed by Roche of Switzerland, the ligand V1A-2303 (8), which targets V1a, was designed and its pharmacological properties were evaluated... Our research indicated [18F]8 as a valuable tool for noninvasively studying V1a receptors in peripheral organs and as a foundational element for the development of next-generation, brain-penetrant ligands specifically designed for the central nervous system."

Cardiovascular • ABCB1

Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2 | N=29 | Completed | Sponsor: Hoffmann-La Roche | N=16 ➔ 29

Enrollment change • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

A population pharmacokinetics model of balovaptan to support dose selection in adult and pediatric populations. (PubMed, J Pharmacokinet Pharmacodyn) - "A sequence of three stepped-dose daily infusions of 50, 25 and 15 mg over 30 or 60 min was predicted to achieve a target occupancy of ≥ 80% in ≥ 95% of patients over a 3-day period. This model predicts both oral and IV balovaptan exposure across a wide age range and will be a valuable tool to analyze and predict its PK in new indications and target populations, including pediatric patients."

Journal • PK/PD data • Autism Spectrum Disorder • Cardiovascular • CNS Disorders • Genetic Disorders • Ischemic stroke • Mood Disorders • Pediatrics • Post-traumatic Stress Disorder

Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2 | N=16 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed | N=30 ➔ 16

Enrollment change • Trial completion • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

S02 – Improving outcomes in autism – dissecting the neurobiological pathways from genetics to behaviour (ECNP 2023) - "Disappointingly, many high-profile recent trials of initially promising medications like balovaptan or arbaclofen have failed to detect effects...Our work illustrates the importance of considering the interaction of risk and resilience pathways in shaping outcomes and identifying new targets for intervention. > The Symposium is 80 minutes: each of the 4 speakers has 15 minutes to present, followed by 5 minutes of Q and A."

CNS Disorders

Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Efficacy and safety of V receptor antagonists in autism spectrum disorder: A meta-analysis. (PubMed, Int J Dev Neurosci) - "Treatment-emergent adverse effects were not serious and dose dependent. Low doses (<10 mg) of V receptor antagonist may be effective in reducing the core symptoms of ASD compared to placebo; however, future active-controlled clinical trials are necessary to generate conclusive evidence."

Clinical • Journal • Retrospective data • Review • Autism Spectrum Disorder • Genetic Disorders

Study to Evaluate The Safety and Efficacy of Balovaptan in Participants With Acute Ischemic Stroke at a High Risk of Developing Malignant Brain Edema (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Hoffmann-La Roche | N=108 ➔ 0 | Trial completion date: Jun 2024 ➔ Nov 2022 | Recruiting ➔ Withdrawn | Trial primary completion date: Jun 2024 ➔ Nov 2022

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Brain Cancer • Cardiovascular • CNS Disorders • Ischemic stroke

"Why hasn't Balovaptan been produced yet? Are autistic children not affected by it?" (@AboodAleli)

Vasopressin receptor antagonists: a patent summary (2018-2022). (PubMed, Expert Opin Ther Pat) - "Publishing balovaptan as a possible treatment for autism spectrum disorder (ASD), greatly increased the interest in CNS-acting vasopressin antagonists. In addition, peripherally active selective V2 and dual-acting V1a/V2 antagonists have also been developed. Although clinical trials were unsuccessful in many cases, there is still potential in the research of vasopressin receptor antagonists as shown by several currently ongoing clinical trials."

Journal • Review • Autism Spectrum Disorder • Genetic Disorders

Predictors of placebo response in three large clinical trials of the V1a receptor antagonist balovaptan in autism spectrum disorder. (PubMed, Neuropsychopharmacology) - "Decreased placebo response was predicted by higher baseline Vineland-II 2DC (i.e., more advanced adaptive function), longer trial duration, and European (vs United States) sites, while increased placebo response was predicted by commercial (vs academic) sites, attention deficit hyperactivity disorder and depression. Identification of these factors may be useful in anticipating and mitigating placebo response in drug development efforts in ASD and across developmental and psychiatric conditions."

Clinical • Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Depression • Genetic Disorders • Psychiatry

Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Hoffmann-La Roche | N=252 ➔ 30

Enrollment change • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Study to Evaluate The Safety and Efficacy of Balovaptan in Participants With Acute Ischemic Stroke at a High Risk of Developing Malignant Brain Edema (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • Brain Cancer • Cardiovascular • CNS Disorders • Ischemic stroke

Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2 | N=252 | Recruiting | Sponsor: Hoffmann-La Roche | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial. (PubMed, JAMA Psychiatry) - P2 | "Further development of robust, sensitive, and objective outcome measures may help to improve future studies in the assessment of therapies targeting communication and socialization in pediatric ASD. ClinicalTrials.gov Identifier: NCT02901431."

Clinical • Journal • Autism Spectrum Disorder • Genetic Disorders • Pediatrics

Large multicenter randomized trials in autism: key insights gained from the balovaptan clinical development program. (PubMed, Mol Autism) - "Taken together, the balovaptan clinical development program has advanced our understanding of the key challenges facing ASD treatment research. The insights gained can be used to inform and improve the design of future clinical trials with the collective aim of developing efficacious therapies to support individuals with ASD."

Journal • Autism Spectrum Disorder • Genetic Disorders

Study to Evaluate The Safety and Efficacy of Balovaptan in Participants With Acute Ischemic Stroke at High Risk of Developing Malignant Brain Edema (clinicaltrials.gov) - P2 | N=108 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • Brain Cancer • Cardiovascular • CNS Disorders • Ischemic stroke

Study To Evaluate The Efficacy And Safety Of Balovaptan In Adults With Post-Traumatic Stress Disorder (PTSD) (clinicaltrials.gov) - P2 | N=252 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder

Study to Evaluate The Safety and Efficacy of Balovaptan in Patients With Acute Ischemic Stroke at High Risk of Developing Malignant Brain Edema (clinicaltrials.gov) - P2 | N=108 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P2 trial • Brain Cancer • Cardiovascular • CNS Disorders • Ischemic stroke

A Study to Evaluate the Safety and Ability of Balovaptan to Reduce the Risk of Severe Brain Swelling in Patients with Acute Ischemic Stroke Estudio para evaluar la seguridad y la capacidad del balovaptán para reducir el riesgo de inflamación cerebral grave en pacientes con accidente cerebrovascular isquémico agudo (clinicaltrialsregister.eu) - P2 | N=108 | Ongoing | Sponsor: Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd

New P2 trial • Brain Cancer • Cardiovascular • Ischemic stroke

Efficacy and safety of balovaptan for socialisation and communication difficulties in autistic adults in North America and Europe: a phase 3, randomised, placebo-controlled trial. (PubMed, Lancet Psychiatry) - P3 | "Balovaptan did not improve social communication in autistic adults. This study provides insights into challenges facing autism spectrum disorder trials, including the considerable placebo response and the selection of appropriate outcome measures."

Journal • P3 data • Autism Spectrum Disorder • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Infectious Disease • Insomnia • Mood Disorders • Pain • Psychiatry • Respiratory Diseases • Schizophrenia • Sleep Disorder • Suicidal Ideation

A Phase 2 Randomized Controlled Trial (RCT) of Balovaptan (BAL) in Pediatric Participants With Autism Spectrum Disorder (ASD) (ACNP 2021) - P2 | "No difference was seen between BAL 10 mg vs PBO in any efficacy measures. No BAL exposure–response relationship was seen. BAL and PBO had similar types and frequencies of adverse events."

Clinical • P2 data • Alzheimer's Disease • CNS Disorders