Bust for Balovaptan in Treatment of Childhood Autism

An oral selective vasopressin 1a (V1a) receptor antagonist failed at improving socialization and communication among those with pediatric autism spectrum disorder (ASD) in a randomized, double-blind study.

When compared with placebo, balovaptan was not significantly more likely to improve this composite endpoint by the end of week 24 (P=0.91). There was also no improvement in secondary endpoints such as week-12 results or individual measures of socialization and communication, according to the phase II aV1ation trial published in JAMA Psychiatry.

Balovaptan’s lack of benefit in pediatric ASD therefore echoes the disappointing results in adults in the phase III V1aduct trial.

Nevertheless, adult-dose balovaptan was well tolerated by children and teenagers 5 years and older in aV1ation. Similar proportions of the experimental and control groups reported adverse reactions (76.7% vs 75.3%) and serious adverse events (1.2% vs 4.9%), Eric Hollander, MD, from the Albert Einstein College of Medicine in New York City, and colleagues found.

Their report comes after another study last year failed to show any therapeutic benefits from intranasal oxytocin for ASD symptoms. Children and teens in that study scored the same as placebo after a 24-week trial period.

ASD is a neurodevelopmental condition defined by lifelong difficulties in social communication and interaction, as well as restrictive or repetitive behaviors. The estimated prevalence of ASD is on the rise in the U.S., affecting approximately 3.14% of children and adolescents from 2019 to 2020.

Genetic and environmental influences on ASD are still poorly understood, and there remain no FDA-approved medications for the core ASD symptoms.

For Hollander and colleagues, it doesn’t have to be the end of the road for balovaptan in autism.

“The heterogeneity across autistic individuals may mean that there is no one-size-fits-all treatment. For example, genetic variation in V1a receptors has been observed, and it is possible that participants’ response to balovaptan may vary depending on their genetic background; however, future studies are required to determine the relationship between these factors,” they wrote.

The aV1ation study was a randomized, double-blind, 24-week parallel-group, placebo-controlled phase II trial. Individuals were screened and randomized between November 2016 and September 2019 across 41 sites in the U.S.

Eligible participants were children with ASD who were ages 5 to 17 years with an I.Q. of 70 or greater. Exclusion criteria included unstable or uncontrolled clinically significant psychiatric or neurologic disorders, or suicidal behavior.

Participants in the investigational group had started out receiving age-adjusted balovaptan doses equivalent to 10-mg or 4-mg adult doses. The 4-mg adult equivalent dose was discontinued during the study due to exposures lower than targeted levels at an interim analysis.

Of the 599 individuals screened, 339 made it to randomization, of whom 167 were ultimately included in the main analysis (mean age 12.1 years and 83.2% boys). The primary endpoint was change on the Vineland-II two-domain composite score for socialization and communication from baseline to week 24.

The authors acknowledged that they had a very strong placebo response, with both groups experiencing similar improvements in ASD symptoms. Placebo-assigned patients in aV1ation may have been susceptible to expectation bias due to a demanding study schedule and knowledge of balovaptan’s breakthrough therapy designation by the FDA, they suggested.

Furthermore, they referenced pediatric depression studies in which the type of participating site appears to factor into the magnitude of a placebo response. The study’s primary analysis population was roughly split between those recruited from academic research sites and those from private clinical research centers.

Hollander and colleagues complained that the currently available measures of outcomes and symptoms in ASD are subject to limitations and bias. The Vineland Adaptive Behavior scale is no exception, given how heavy of an influence caregiver reports can have on results.

They recommend further studies that use more objective measures to assess therapies targeted at communication and socialization in pediatric ASD. These might include quantifiable digital biomarkers, behavioral tasks performance, electroencephalograms, and eye tracking, they suggested.

  • James Lopilato is a staff writer for Medpage Today. He covers a variety of topics being explored in current medical science research.


The study was supported by F. Hoffmann-La Roche.

Hollander reported receiving research grants from the U.S. Department of Defense, the FDA, GW Pharma, F. Hoffmann-La Roche; editorial stipends from Elsevier; and serving on scientific advisory boards for GW Pharma and F. Hoffmann-La Roche.

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