APATURA: a Phase 2a study of elarekibep, an inhaled IL-4 receptor alpha inhibitor, in moderate-to-severe asthma

<bold>Background:</bold> Elarekibep (AZD1402/PRS-060) is an inhaled Anticalin® protein engineered to inhibit IL-4 receptor alpha signaling, a clinically validated asthma target. <bold>Methods:</bold> A two-part Phase 2a randomized, double-blind, placebo-controlled, dose ranging study in adults (<ext-link>NCT04643158</ext-link>). Part 1 evaluated safety and PK following 28 days twice daily dosing with dry powder formulated elarekibep (1, 3, 10mg) or placebo in controlled patients (ACQ-6 ≤ 1.0) on a stable medium ICS-LABA dose. Part 2 evaluated efficacy of elarekibep (1, 3mg) versus placebo following twice daily dosing for 28 days in a T2-high, uncontrolled moderate-severe asthma population. <bold>Results:</bold> 72 patients randomized (Part 1: n=50; Part 2: n=22). No clinical safety concerns were reported; the study was stopped early due to new non-clinical findings. Treatment-emergent adverse events were reported for 56.0% (elarekibep, 58.8%; placebo, 50.0%) of patients in Part 1 and 63.6% (elarekibep, 61.5 %; placebo, 66.7%) in Part 2. One SAE, in the 3mg group, was reported during follow up. After inhalation, elarekibep was steadily absorbed (Tmax 3-4 hours) with an elimination half-life ranging between 8-20 hours. Treatment emergent ADAs were detected in 83% (n= 38/46) of elarekibep exposed individuals with no impact on PK characteristics. At Week 4, the LS mean increase (95% CI) in prebronchodilator FEV1 of the 3mg elarekibep group was 196ml (14.3; 378) compared to placebo. <bold>Conclusions:</bold> Elarekibep was clinically well-tolerated with no identified short-term safety concerns. Due to early study termination, firm conclusions about efficacy could not be drawn. Clinical development has been discontinued due to pre-clinical findings.