MapLight Therapeutics Announces ML-004 Autism Study Results

MapLight Therapeutics announced topline results from IRIS, a Phase 2 study of ML-004 in autism spectrum disorder, or ASD. The study randomized 161 participants with prespecified analyses planned by age group and baseline irritability severity. As an exploratory signal-finding Phase 2 study, IRIS was designed to test multiple clinical endpoints based on preclinical findings, including social communication and irritability, and to identify the most appropriate development path forward. The study did not meet its primary endpoint of change from baseline to Week 12 in the caregiver-reported Autism Behavioral Inventory-Social Communication Domain score. Social communication is a domain for which no approved pharmacologic therapies exist, and for which validated, treatment-sensitive outcome measures remain an area of active scientific investigation. However, in a prespecified analysis of adolescents with moderate or greater baseline irritability, ML-004 demonstrated a clinically meaningful improvement in irritability over placebo as measured by change from baseline in the care-partner reported ABC-I subscale. Consistent with this finding, clinically meaningful improvement over placebo was observed on the Clinician Global Impression-Improvement-Irritability domain in the adolescent population randomized with moderate or greater baseline irritability. The treatment effects on the ABC-I and CGI-I irritability domain were more pronounced among adolescents with greater baseline irritability. In the total population of participants with baseline ABC-I score greater than16, ML-004 demonstrated an effect size of 0.64 on the key secondary endpoint of change from baseline in the ABC-I score at week 12. ML-004 was generally well-tolerated, with treatment-emergent adverse events that were all mild to moderate in severity. Adolescents experienced fewer TEAEs than adults. There were no SAEs or severe AEs reported in the ML-004 treated participants; among placebo-treated participants, two experienced a severe TEAE and one experienced a serious adverse event. In the randomized population, the most common TEAEs were headache, nausea, somnolence, vomiting, fatigue, and dizziness. No events of extrapyramidal TEAEs were observed with active treatment. The mean weight gain over the course of the study was lower for ML-004 than placebo. In adolescents, the most common adverse events were headache, somnolence, nausea and vomiting. Two adolescents in the active arm discontinued the study due to an adverse event.