Data from two phase 2 clinical trials published in Science Translational Medicine showed that modulating the hormone vasopressin’s biological pathway may improve social functioning in adults and children with autism spectrum disorder.
“Although the etiology of ASD is complex and multifactorial, involving genetic and environmental factors, several neural pathways and circuits underlying social behavior have been identified. The neuropeptide vasopressin has been implicated in modulation of brain circuits regulating social behaviors,” Federico Bolognani, MD, PhD, from F. Hoffmann–La Roche Ltd., Switzerland, and colleagues wrote.
Bolognani and colleagues examined whether balovaptan, an oral selective vasopressin V1a receptor antagonist, could be a potential therapeutic target for the treatment of ASD in 223 adult men.
The researchers evaluated three doses of balovaptan — 1.5 mg, 4 mg and 10 mg —administered daily for 12 weeks compared with placebo in 223 adult men with ASD and an IQ of 70 or more. They examined the safety and tolerability of balovaptan as well as its effect on social communication and social interaction deficits.
Overall, 32 participants were randomized to receive 1.5 mg of balovaptan, 77 received 4 mg, 39 received 10 mg and 75 received placebo.
Balovaptan treatment did not lead to a change from baseline compared with placebo at 12 weeks in the Social Responsiveness Scale, 2nd Edition (SRS-2), the primary endpoint.
However, the results showed participants treated with balovaptan 4 mg or 10 mg had clinically meaningful improvements on the Vineland-II Adaptive Behavior Scales composite score compared with placebo. This improvement was mainly attributable to improvements in socialization and communication scores, according to the study.
Balovaptan was well-tolerated and there were no reported drug-related safety issues, the results showed.
The other phase 2 study, conducted by Karen J. Parker, PhD, from the department of psychiatry and behavioral sciences at Stanford University, and colleagues, also targeted the vasopressin system, though in pediatric patients with ASD.
Parker and colleagued tested the efficacy and tolerability of 4-week intranasal administration of arginine vasopressin (AVP) in 30 children with ASD aged 6 to 12 years to determine the change from baseline in social ability, as measured by parent ratings on the SRS-2 total score. They also examined change from baseline in social communication, social cognition abilities and other core/related symptoms of ASD.
The results showed that children with ASD treated with intranasal arginine vasopressin for 4 weeks had greater improvement in their social behavior compared with those treated with placebo as measured by the SRS-2 score (P = .0052) as well as the Clinical Global Impression–Improvement scale (P = .0145). In addition, participants who received vasopressin showed improvement in their ability to interpret the mental/emotional states of others and increased facial emotion recognition abilities compared to those who received with placebo.
“On nearly all behavioral measures, participants with the highest pretreatment blood AVP concentrations benefitted the most from AVP treatment, suggesting that pretreatment blood AVP concentrations may be useful for setting dosing guidelines for this medication,” Parker and colleagues wrote.
Vasopressin also reduced anxiety symptoms compared to placebo, according to the results. Overall, arginine vasopressin was well-tolerated and had minimal adverse effects.
“Although using different therapeutic strategies, both the Parker et al. study and our ... trial point to a central role of vasopressin in modulating social behavior in ASD,” Bolognani and colleagues wrote. “Future larger and well-controlled studies in adults and children with ASD will shed further light on the potential usefulness of targeting the vasopressin pathway to address socialization and communication challenges and potentially pave the way for the development of a new pharmacological treatment for these core symptoms of ASD.” – by Savannah Demko
Disclosures: Bolognani and colleagues are all employees of F. Hoffmann–La Roche. Please see the study for all other authors’ relevant financial disclosures. Parker reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.