Pimavanserin Trial Finds No Efficacy Signal in Irritability in Pediatric ASD

Key Takeaways

• In pediatric ASD, neither low-dose nor high-dose pimavanserin differed significantly from placebo on week-6 caregiver-rated ABC-I change.
• No secondary endpoint showed a statistically significant difference between pimavanserin and placebo groups.
• Treatment-emergent adverse events were similar across groups, and no serious treatment-emergent adverse events or deaths occurred.

In a phase 2 randomized trial of pimavanserin in ASD irritability, children and adolescents with autism spectrum disorder-associated irritability did not differ from placebo on the week-6 primary outcome, while pimavanserin was well tolerated.

The phase 2 study, published in the Journal of the American Academy of Child & Adolescent Psychiatry, used 1:1:1 randomization to low-dose pimavanserin, high-dose pimavanserin, or placebo. It focused on children and adolescents with irritability associated with autism spectrum disorder. Ages 5-12 years received 10 mg/day or 20 mg/day, and ages 13-17 years received 20 mg/day or 34 mg/day. Treatment continued for 6 weeks with a 30-day follow-up, and the primary endpoint was week-6 change from baseline in the caregiver-rated ABC-I subscale. Of those completing double-masked treatment, 76 were in the low-dose group, 78 were in the high-dose group, and 78 received placebo.

Placebo produced a least-squares mean ABC-I improvement of -9.6, with a 95% confidence interval from -11.7 to -7.5. Low-dose pimavanserin showed -11.2, with a 95% confidence interval from -13.3 to -9.0, and high-dose pimavanserin also showed -11.2, with a 95% confidence interval from -13.3 to -9.1. Secondary measures included CGI-Severity irritability, CGI-Improvement irritability, Repetitive Behavior Scale-Revised, Vineland Adaptive Behavior Scales socialization, and the Caregiver Strain Questionnaire. Both active-dose changes remained close to placebo, and neither dose differed significantly on the primary endpoint. No statistically significant between-group differences emerged on any prespecified secondary endpoint over the 6-week treatment period.

Treatment-emergent adverse events occurred at similar frequencies across groups. They were reported in 39 placebo patients (50.0%), in 36 low-dose patients (46.8%), and in 43 high-dose patients (53.1%). No serious treatment-emergent adverse events or deaths occurred during the trial.

Investigators concluded that pimavanserin was well tolerated in this short-term randomized study, but efficacy for irritability in children or adolescents with autism spectrum disorder was not demonstrated compared with placebo.