Aclaris Reports Phase 2b ATI-1777 Trial Outcomes for Atopic Dermatitis

A recent study has shed light on the potential of a novel treatment for atopic dermatitis (AD), a chronic skin condition characterized by inflammation and itchiness. The research, conducted by Aclaris Therapeutics, Inc., a biopharmaceutical firm at the forefront of developing innovative drugs for immuno-inflammatory disorders, has revealed promising results from its Phase 2b clinical trial of ATI-1777. This drug candidate is an experimental topical "soft" JAK 1/3 inhibitor, designed to offer a new approach to managing mild to severe AD.

The Phase 2b trial, designated as ATI-1777-AD-202, was a randomized, double-blind, and vehicle-controlled study. It aimed to assess the efficacy, safety, tolerability, and pharmacokinetics of different concentrations of ATI-1777, administered twice daily at 0.5%, 1%, and 2%, and once daily at a single 2% concentration. Notably, the trial involved an emollient-containing spray formulation of ATI-1777 and included 250 participants with varying degrees of AD, ranging from mild to severe. The study was conducted across 30 clinical trial sites in the United States and included both adults and children as young as 12 years old.

Dr. Neal Walker, Chairman of Aclaris’ Board of Directors, highlighted the significance of the trial's findings. He noted that the efficacy, pharmacokinetic profile, and safety results were in line with those observed in the Phase 2a trial. The drug demonstrated response rates comparable to existing market treatments, coupled with a distinct safety profile due to its minimal systemic absorption. This was particularly notable given the higher vehicle response and the inclusion of milder patient cases during the trial.

The primary efficacy endpoint of the trial was the percent change from baseline in the Eczema Area and Severity Index (EASI) score at week 4. The 2% BID treatment of ATI-1777 showed statistical significance compared to the vehicle group, with a 69.7% versus 58.7% reduction (p=0.035). Although not statistically superior, the 2% QD treatment also showed a trend toward significance. In the per-protocol population, the 2% BID treatment demonstrated a 70.8% reduction in EASI compared to a 58.5% reduction in the vehicle group (p=0.025). A post-hoc analysis focusing on patients with moderate or severe AD at baseline revealed a significant reduction in EASI scores for both the 2% BID and QD treatments.

Furthermore, the drug showed improvements in the proportion of patients who achieved an IGA-TS response, a regulatory endpoint set by the U.S. FDA. Pharmacokinetic analysis indicated minimal exposure to ATI-1777, with 97% of plasma samples from dosed patients having concentrations below 1/10th of the IC50. The drug was well-tolerated, with no adverse events commonly associated with JAK inhibitors observed. Common adverse events were nasopharyngitis and application site itch, both reported in a small percentage of patients.

Douglas Manion, M.D., Aclaris’ Chief Executive Officer, expressed gratitude to all involved in the trial and reiterated the company's intention to seek a development and commercialization partner for ATI-1777, potentially expanding its use to other indications such as vitiligo. Aclaris plans to present the full results at a forthcoming scientific conference.

The study underscores the potential of ATI-1777 as a "soft" topical JAK inhibitor for treating AD, offering a new option for patients in need of effective and well-tolerated treatments. The convenience of a spray formulation and the possibility of once-a-day dosing could provide additional benefits, enhancing patient compliance and quality of life.