Aclaris announces Phase 2b study of ATI-1777 met primary efficacy endpoint

Aclaris Therapeutic announced top-line results from its Phase 2b study of ATI-1777, an investigational topical “soft” JAK 1/3 inhibitor, in patients with mild to severe atopic dermatitis). ATI-1777 was generated from Aclaris’ proprietary KINect drug discovery platform. Results: The trial met the primary efficacy endpoint, the percent change from baseline in the Eczema Area and Severity Index score at week 4, with statistical significance for patients treated with ATI-1777 2% BID compared to patients treated with vehicle. In addition, the following results were observed with respect to the primary endpoint: While not statistically superior, ATI-1777 2% QD showed a trend toward significance; In the per-protocol population, or all patients who had week 4 data with no major protocol deviations, ATI-1777 2% BID demonstrated a 70.8% reduction in EASI compared to a 58.5% reduction in vehicle, and ATI-1777 2% QD demonstrated a 68.4% reduction in EASI compared to a 59.7% reduction in vehicle. In addition, a post-hoc analysis of only patients who had baseline severity of moderate or severe AD showed a 65.6% and 65.1% reduction in the EASI score at week 4 in ATI-1777 2% BID and ATI-1777 2% QD, respectively, compared to a 52.6% reduction in the pooled vehicle group. While not statistically powered, ATI-1777 2% BID and 2% QD also showed improvement in the proportion of patients who reached an IGA-TS response at week 4. The per-protocol population demonstrated an IGA-TS response at week 4 of 41.8% for ATI-1777 2% BID compared to 25.5% in vehicle and 39.8% for ATI-1777 2% QD compared to 25.4% in vehicle. A PK analysis showed minimal levels of exposure to ATI-1777. The mean steady state trough drug levels at week 4 were 0.319 ng/mL, representing 0.7% of IC50 for JAK 1/3 inhibition in whole blood. In total, 97% of ATI-1777 plasma samples from dosed patients had concentrations below 1/10th of the IC50, and six samples of 570 samples analyzed had concentrations above 1/4 of the IC50. No meaningful safety findings were observed and ATI-1777 was well tolerated.