PBF-680, an oral A1 adenosine receptor antagonist, inhibits the late allergic response (LAR) in mild-to-moderate atopic asthmatics: a Phase-IIa trial

Abstract

Background: PBF-680 is an oral A1 adenosine receptor antagonist in development for asthma.

Aims and Objectives: To evaluate PBF-680 efficacy to inhibit the LAR, a standard goal for asthma therapies development.

Methods: Double-blind, randomized, cross-over trial with once-daily 10-mg PBF-680 or placebo for 5 days, on 8 atopic asthmatics on withdrawn low-to-medium-dose inhaled corticosteroid, showing both early allergic response (EAR, ≥20% FEV₁ drop) and LAR (FEV₁ drop ≥15% at 3-10h post-aeroallergen challenge). The primary outcome was the LAR area under the FEV₁ curve (AUC_3-10h). Data analysis: repeated-measures general linear model or Kruskal-Wallis/Wilcoxon.

Results: LAR AUC_3-10h was (mean ± standard error [SEM]) -64.84±14.14 (placebo), and 13.71±13.61 (PBF-680; P<0.001 vs. placebo,

Fig. 1). EAR was -26.3% FEV₁ drop (placebo) and -20.0% (PBF-680, P=0.049 vs. placebo). Exhaled breath nitric oxide fraction (FeNO, ppb) was 34.0±2.5 (placebo) and 19.7±3.0 (PBF-680, P=0.042 vs. placebo). Blood eosinophils/mcL were 283±64 (placebo) and 60±13 (PBF-680, P=0.01 vs. placebo). No relevant adverse events were recorded.

Conclusions: In mild-to-moderate asthmatics, PBF-680 abrogated the LAR, and reduced the EAR, FeNO, and, remarkably, blood eosinophils, with correct safety profile. The data position the adenosine modulator PBF-680 as a promising oral asthma therapy.

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