PBF-680, an oral A1 adenosine receptor antagonist, increases trough forced expiratory volume in 1 second (FEV1) in mild-to-moderate asthma: a Phase-II trial

<bold>Background:</bold> Adenosine is involved in bronchoconstriction and airway inflammation. PBF-680 is a novel oral A1 adenosine receptor antagonist in development for asthma. <bold>Aims and objectives:</bold> To evaluate PBF-680 efficacy to increase trough FEV₁ in asthma. <bold>Methods:</bold> Double-blind, randomized, parallel-arm, multicenter trial comparing 15-day PBF-680 10-mg versus placebo on 63 mild-to-moderate atopic asthmatics with a positive bronchodilator test and baseline pre-bronchodilator FEV₁ ≥60% and ≤90% of predicted upon LABA and ICS weaning. The primary outcome was trough FEV₁ change from baseline on day 16, defined as the mean FEV₁ at 23h15min and 23h45min post-dose. Data analysis: repeated-measures general linear model, alpha=0.1 (<italic>P</italic><0.1 was significant). <bold>Results:</bold> The study met its primary endpoint. PBF-680 produced a 180-mL mean trough FEV₁ increase over placebo (placebo trough FEV₁ was 2.88±0.10 [L, mean ± standard deviation] versus 3.06±0.09 PBF-680; <italic>P</italic>=0.0816). PBF-680 also improved the Asthma Control Questionnaire (ACQ)-7 significantly. As an exploratory outcome, PBF-680 decreased the blood eosinophils (eos) on day 15 (absolute change from baseline of -184.7±204.5 [PBF-680] versus 49.3±136.5 [placebo] eos/mcL, <italic>P</italic><0.0001. No clinically relevant adverse events were reported. <bold>Conclusions:</bold> A 15-day course of 10-mg PBF-680 increases trough FEV₁ in mild-to-moderate asthmatics, with an excellent safety profile. Remarkably, PBF-680 significantly reduces circulating eosinophils. These data support the potential of PBF-680 as a promising oral anti-inflammatory asthma therapy. <bold>Funding:</bold> Palobiofarma S.L., Spain