Aclaris Therapeutics Announces Top-line Results from 4-Week Phase 2b Trial of ATI-1777 for Mild to Severe Atopic Dermatitis - Seite 2

• While not statistically superior, ATI-1777 2% QD showed a trend toward significance (68.3% compared to 59.5% in vehicle, p=0.086).
• 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 (p=0.025), and ATI-1777 2% QD demonstrated a 68.4% reduction in EASI compared to a 59.7% reduction in vehicle (p=0.102).
• 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 (p=0.029 and 0.040, respectively).
  

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 (Investigator Global Assessment Treatment Success, the U.S. FDA regulatory endpoint) at week 4 (ATI-1777 2% BID: 37.2% compared to 27.1% in vehicle, p=0.141; ATI-1777 2% QD: 36.6% compared to 26.3% in vehicle, p=0.137). 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 (p=0.059) and 39.8% for ATI-1777 2% QD compared to 25.4% in vehicle (p=0.079).

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 (from five ATI-1777-treated patients) of 570 samples analyzed had concentrations above 1/4 of the IC₅₀.

No meaningful safety findings were observed and ATI-1777 was well tolerated. In particular, no adverse events (AEs) commonly associated with JAK inhibitors, including serious infections, malignancies, major adverse cardiovascular events (MACE) and thromboses, were observed in patients treated with ATI-1777. The most common AEs in patients treated with ATI-1777 (reported in ≥2% patients) were nasopharyngitis (ATI-1777: 2%; vehicle: 2%) and application site itch (ATI-1777: 2.5%; vehicle: 0%). Among patients receiving ATI-1777, there were no discontinuations due to AEs and one serious but unrelated AE in a patient (ATI-1777 2% QD) who completed the study. All other AEs were mild to moderate in severity.