Efficacy and safety of LAU-7b in a Phase 2 trial in adults with cystic fibrosis.

Background: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF.
Methods: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF. LAU-7b or placebo was administered over 24 weeks as six 21-day treatment cycles each separated by 7 days. The primary efficacy endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV ₁ ) at 24 weeks.
Results: A total of 166 subjects received at least one dose of study drug (Intent-To-Treat population, ITT), of which 122 received ≥5 treatment cycles (Per-Protocol population, PP). Both treatment arms showed a mean lung function loss at 24 weeks of 1.18 ppFEV ₁ points with LAU-7b and 1.95 ppFEV ₁ with placebo, a 0.77 ppFEV ₁ (40 s) difference, p=0.345, and a 0.95 ppFEV ₁ (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV ₁ through 24 weeks showed differences of 1.01 and 1.23 ppFEV ₁ , in the ITT (65 % less loss, p=0.067) and PP populations (78 % less loss, reaching statistical significance p=0.049), respectively. LAU-7b had an acceptable safety profile.
Conclusion: Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development.
Competing Interests: Declaration of competing interest MW Konstan, LC Lands, D Potvin and D Radzioch report receiving consulting fees from Laurent Pharmaceuticals; JM Houle, R Pislariu, P Colin, I Kianicka are employees of Laurent Pharmaceuticals; D Polineni, J Chmiel, L Bilodeau, PG Middleton, E Matouk, T Kotsimbos, JB Zuckerman, SZ Nasr, TG Liou report no conflict of interest related to this study.
(Copyright © 2024. Published by Elsevier B.V.)