An Inhaled PI3Kδ Inhibitor Improves Recovery in Acutely Exacerbating COPD Patients: A Randomized Trial

• DOI: 10.2147/copd.s309129
• Publication Date: 2021-06-02T21:04:24Z
• Authors: Anthony Cahn; J Nicole Hamblin; Jon Robertson; Malcolm Begg; Emily Jarvis; Robert Wilson; Gordon Dear; Claudia Leemereise; Yi Cui; Maki Mizuma; Mickael Montembault; Cedric Van Holsbeke; Wim Vos; Wilfried De Backer; Jan De Backer; Edith M Hessel
• Keywords: RC705-779; nemiralisib; copd; Bayes Theorem; International Journal of Chronic Obstructive Pulmonary Disease; Bronchodilator Agents; 3. Good health; Diseases of the respiratory system; Phosphatidylinositol 3-Kinases; Pulmonary Disease, Chronic Obstructive; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Double-Blind Method; Forced Expiratory Volume; Administration, Inhalation; Humans; Human medicine; acute exacerbation; Original Research

This study evaluated the safety and efficacy of inhaled nemiralisib, a phosphoinositide 3-kinase δ (PI3Kδ) inhibitor, in patients with an acute exacerbation chronic obstructive pulmonary disease (COPD).In this double-blind, placebo-controlled study, 126 (40-80 years post-bronchodilator forced expiratory volume 1 sec (FEV1) ≤80% predicted (previously documented)) were randomized 1:1 to once daily nemiralisib (1 mg) or placebo for 84 days, added standard care. The primary endpoint was specific imaging airway (siVaw) after 28 treatment days analyzed using Bayesian repeated measures model (clintrials.gov: NCT02294734).A total treatment; 55 on active 49 completed study. When comparing placebo-treated patients, 18% placebo-corrected increase from baseline distal siVaw (95% credible intervals (Cr I) (-1%, 42%)) observed Day 28. probability that true ratio >0% (Pr(θ>0)) 96%, suggestive real effect. Improvements across all lung lobes. Patients treated experienced 107.3 mL improvement posterior median FEV1 (change baseline, 95% Cr I (-2.1, 215.5)) at day 84, compared placebo. Adverse events reported by 41 most common being post-inhalation cough (35%) vs (3%).These data show addition usual care delivers more effective recovery improves function parameters including FEV1. Although identified, otherwise well tolerated, providing promising novel therapy acutely ill patient group.