お知らせ • Jun 22
MapLight Therapeutics Announces Topline Results from Phase 2 IRIS Study for ML-004 in Autism Spectrum Disorder
MapLight Therapeutics, Inc. announced topline results from IRIS (ML-004-002), a Phase 2 study of ML-004 in autism spectrum disorder (ASD). The study randomized 161 participants (102 adolescents, 59 adults), with prespecified analyses planned by age group and baseline irritability severity. As an exploratory signal-finding Phase 2 study, IRIS was explicitly 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 (ABI)–Social Communication Domain score. However, in a prespecified analysis of adolescents (age 12–17) with moderate or greater baseline irritability (double-blind baseline ABC-I score >16, N=20), 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 (LS mean difference vs. Placebo -9.58, ES=1.33, nominal p value=0.013). Consistent with this finding, clinically meaningful improvement over placebo was observed on the Clinician Global Impression-Improvement (CGI-I) -Irritability domain in the adolescent population randomized with moderate or greater baseline irritability (LS mean difference -0.63; ES=1.08, nominal p value=0.036). 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 (age 12-45) with baseline ABC-I score >16 (N=26), ML-004 demonstrated an effect size of 0.64 (nominal p-value =0.13) 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 (TEAEs) that were all mild to moderate in severity. Adolescents experienced fewer TEAEs than adults (Adolescent TEAEs: 62.7% for ML-004 versus 41.2% for placebo; Adult TEAEs: 86.7% for ML-004 versus 72.4% for placebo). 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 (>5% in ML-004 arm and >placebo) 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 (occurring in =5% of ML-004-treated adolescents and at least twice the rate of placebo) were headache (13.7% vs. 3.9%), somnolence (11.8% vs. 0%), nausea (9.8% vs. 0%), and vomiting (5.9% vs. 0%). Two (3.9%) adolescents in the active arm discontinued the study due to an adverse event (0% for placebo). ML-004 is an immediate-release, or IR, and extended-release, or ER, formulation of zolmitriptan, a 5-HT1B/1D agonist currently approved for the acute treatment of migraine. The Phase 2 IRIS trial (NCT05081245) is a randomized, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of ML-004 in adults (age 18-45) and adolescents (age 12-17) with autism spectrum disorder. A total of 161 participants were randomized, inclusive of 102 adolescents. Following a full review of the data, the Company expects to engage with the U.S. Food and Drug Administration (FDA) in an End-of-Phase 2 meeting to determine the clinical development path forward. The Company remains well capitalized ahead of the topline results from its Phase 2 ZEPHYR trial evaluating ML-007C-MA in schizophrenia, expected by mid-August 2026.