Aclaris’s ATI-2138 Yields 77% EASI Reduction and 65% DLQI Gain
In an open-label Phase 2a trial, Aclaris Therapeutics’ oral ITK/JAK3 inhibitor ATI-2138 achieved a 77% reduction in Eczema Area and Severity Index at week 12 in moderate-to-severe atopic dermatitis patients. The treatment also delivered 70% body surface area improvement, 50% itch reduction, 55% POEM gain and 65% DLQI gain with near complete target occupancy and good tolerability.
1. Phase 2a Trial Design
The open-label, single-arm Phase 2a study evaluated 10 mg of ATI-2138 administered twice daily for 12 weeks in adults with moderate-to-severe atopic dermatitis. Primary endpoints focused on safety and tolerability, while secondary endpoints included pharmacodynamic assessments and efficacy measures such as EASI, PP-NRS, POEM and DLQI scores.
2. Efficacy Outcomes
At week 12, patients receiving low-dose ATI-2138 experienced a 77% improvement in Eczema Area and Severity Index, a 70% reduction in affected body surface area, a 50% decrease in peak pruritus intensity on the PP-NRS, a 55% improvement on the POEM scale and a 65% gain in DLQI.
3. Safety Profile and Mechanism
ATI-2138 was well tolerated with no dose-limiting toxicities, and near complete ITK target occupancy was observed across the dosing interval. Biomarker analyses indicated modulation of Th1, Th2, Th17, fibrotic and T cell activation pathways, supporting its potential as a low-burden, best-in-class immuno-inflammatory therapy.