Late Breaking Abstract - Phase 2 trial evaluating the effects of dexpramipexole on blood eosinophils, lung function, and airway biomarkers in eosinophilic asthma

Abstract

Background: Dexpramipexole is an oral drug that depletes eosinophils by inhibiting their maturation.

Objectives: Evaluate the safety and efficacy of dexpramipexole in subjects with poorly controlled moderate-severe eosinophilic asthma with absolute eosinophil count (AEC) ≥0.30x10⁹/L.

Methods: AS201 was a randomized, double-blind, placebo-controlled trial (NCT04046939). 103 subjects were randomized 1:1:1:1 to receive dexpramipexole 75, 150, & 300 mg/day and placebo (PBO) for 12 weeks. The primary endpoint was change in blood AEC from Baseline to Week 12. Secondary endpoints included change from Baseline to Week 12 in pre-bronchodilator (BD) FEV₁. Nasal eosinophil peroxidase (EPX), a measure of tissue eosinophils, was an exploratory endpoint.

Results: At 12 Weeks, AEC was reduced by 79.5% (p<0.001), 69.4% (p=0.001), and 59.7% (p=0.019) in the 300, 150, & 75 mg/day arms, respectively (p values vs. PBO). Dexpramipexole 300 mg/day resulted in a PBO-corrected pre-BD FEV1 change from Baseline of 271 mL (p=0.0083), 182 mL (p=0.0999), and 240 mL (p=0.0242) at Weeks 8, 12 and 16/18, respectively. At Week 12, pre-BD ∆FEV₁ was correlated with ∆AEC, Spearman correlation coefficient -0.58, p<0.001 (combined 300 and 150 mg/day arms). At Week 12, nasal EPX was reduced by 89.0% (p=0.020), 82.6% (p=0.021), 35.5% (p=0.540), and 16.7%, for the 300, 150, & 75 mg/day and PBO arms, respectively (p values relative to PBO). Adverse events were similar between the dexpramipexole-treated and PBO arms.

Conclusions: Dexpramipexole was well-tolerated and effective in lowering eosinophils and improving FEV₁ in a population of poorly controlled moderate-severe asthmatics.