Balovaptan failed to improve socialization, communication in adults with autism

Balovaptan did not improve socialization and communication difficulties in adults with autism spectrum disorder, according to results of a phase 3 randomized, placebo-controlled, double-blind clinical trial published in Lancet Psychiatry.

“Although the cause of autism spectrum disorder is not fully understood, several key brain signaling pathways have been implicated in its development,” Suma Jacob, MD, PhD, associate professor, department of psychiatry at the University of Minnesota, and colleagues wrote. “One such pathway is the vasopressin system. Preclinical evidence suggests that vasopressin can influence social behaviors, such as fear, anxiety, and pair-bonding, via vasopressin 1a (V1a) receptors.”

Jacob and colleagues sought to assess the safety, effectiveness, tolerability and pharmacokinetic profile of balovaptan (RG7314, Roche), a vasopressin 1a receptor antagonist, versus placebo in adults with ASD, as there are no currently approved drug therapies which support treatment of communication and socialization problems in those on the autism spectrum.

The V1aduct study was a phase 3 trial conducted at 46 sites across six countries: U.K., France, Italy and Spain, the U.S. and Canada. The study included 322 participants aged at least 18 years, with an intelligence quotient of 70 or higher and who met the criteria for moderate-to-severe ASD according to the DSM-5.

Participants included 64 women and 257 men, with 260 hailing from North America and 61 from Europe, who were randomly allocated on a 1:1 basis, through either an interactive voice or online response system, to receive 10 mg of balovaptan (164) or placebo (158) each day over 24 weeks. Participants, study site personnel and the sponsor were masked to treatment assignment.

Primary endpoint for the study was any measurable alteration in Vineland-II 2DC score from baseline to study interval conclusion. Primary analysis was done with ANCOVA in the intention-to-treat population.

Data showed that 115 participants discontinued treatment before study conclusion; that included 60 from the balovaptan group and 55 in the placebo group.

Mean baseline Vineland-II 2DC scores were 67.2 (SD 15.3) in the balovaptan group and 66.2 (17.7) in the placebo group. Upon study conclusion, the mean change to Vineland-II 2DC scores was 4.56 (SD 10.85) for balovaptan patients and 6.83 (12.18) in the placebo cohort.

Jacob and colleagues found that balovaptan was well tolerated, with the most common adverse events upper respiratory issues, insomnia, oropharyngeal pain and dizziness. Serious adverse events were reported for two participants in the balovaptan group and five in the placebo group. No treatment-related deaths occurred.

“Future studies can use these findings to improve the design of randomized controlled trials of treatments for autism spectrum disorder,” Jacob and colleagues wrote.