Apogee Therapeutics (APGE) Study result summary

Study design and objectives

• APEX Part B was a randomized, dose-ranging phase II trial in 346 moderate-to-severe atopic dermatitis patients, testing low, mid, and high doses of zumilokibart versus placebo to identify the optimal dose for phase III.

• Patients were randomized to dosing intervals of every 3 or 6 months, with only 4 induction doses and 2–4 maintenance doses per year, significantly reducing injection burden.

• The primary endpoint was EASI-75 at week 16, with secondary endpoints including IGA 0/1, EASI-90, EASI-100, and itch NRS reduction.

• The trial population had increased disease severity compared to Part A and was globally representative, with well-balanced baseline demographics.

• The mid-dose regimen was selected for phase III based on efficacy, safety, and reduced injection burden.

Key efficacy results

• Mid-dose zumilokibart achieved 65.9% EASI-75 at week 16, with high-dose showing similar results and low-dose less effective; placebo response was 23.4%.

• Significant improvements were seen in IGA 0/1 (46%), EASI-90 (47.4%), EASI-100 (16.5%), and ≥4-point itch NRS reduction (50.5%) at week 16.

• Lesion reduction was observed as early as week 1, with robust and continuous improvement across all endpoints.

• Efficacy was consistent with Part A and compared favorably to existing biologics and JAK inhibitors in non-head-to-head analyses.

• Maintenance data showed >40% achieving clear skin (EASI-100) at week 52 on every-three-month dosing.

Safety and tolerability

• Zumilokibart was well-tolerated, with adverse events in line with the IL-13/IL-4 class; most common were nasopharyngitis, headache, conjunctivitis, URTI, atopic dermatitis, and UTI.

• Non-infective conjunctivitis rates were 5.9% for the planned phase III dose, with pooled conjunctivitis-related events at 10.6%, similar to standard of care.

• Serious TEAEs and discontinuations due to TEAEs were low and similar to placebo, with an overall discontinuation rate of 6%.

• No effect of anti-drug antibodies on PK, efficacy, or safety was observed.

• UTIs were not considered mechanistically related or clinically concerning.