Late Breaking Abstract - A novel macrolide, EP395, in patients with stable COPD: a RCT

<bold>Background:</bold> EP395, a macrolide with anti-inflammatory properties in preclinical models and negligible antimicrobial activity, is being developed as a potential treatment to reduce exacerbations of COPD. <bold>Aims:</bold> To assess safety and tolerability of 3-months treatment with EP395 in COPD patients, as well as effects on lung and systemic inflammation. <bold>Methods:</bold> In this double-blind, placebo-controlled study (<ext-link>NCT05572333</ext-link>), COPD patients (aged ≥45 years, diagnosed with COPD for ≥2 years, and stable on at least 1 maintenance inhaled therapy) were randomised (2:1) to either 375 mg EP395 or placebo for 12 weeks. Biomarkers of inflammation were assessed in sputum supernatant and serum. <bold>Results:</bold> 61 patients were randomised (42 EP395 and 19 placebo). 12 weeks EP395 treatment was well tolerated: there were no serious adverse events assessed as related to EP395, and adverse events (AE) were reported in similar proportions in the EP395 and placebo groups (64.3% and 63.2%, respectively). 4 patients were withdrawn due to AEs (3 EP395 and 1 placebo). Sputum neutrophil elastase (NE) and myeloperoxidase (MPO), mediators involved in neutrophil activation, were reduced following EP395 treatment (treatment difference [log scale] at the end of dosing: NE −0.415 pg/mL (95% CI [−0.787, ˗0.043] p-value 0.030), and MPO −0.282 pg/mL (95% CI [˗0.640, 0.076] p-value 0.119). Sputum neutrophils (numbers and percentage) were not affected by EP395 treatment. There was a trend for a reduction in serum interleukin-6 (IL-6) following EP395: treatment difference [log scale] was ˗0.289 pg/mL (95% CI [−0.650, 0.073] p-value 0.112). <bold>Conclusions:</bold> EP395 treatment for 3 months was well tolerated and demonstrated effects on inflammation.