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

Michael W. Konstan, Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital, OH, USA.
Deepika Polineni, Washington University School of Medicine, MO, USA.
James F. Chmiel, Indiana University School of Medicine and Riley Hospital for Children at IU Health, IN, USA.
Lara Bilodeau, Institut Universitaire de Cardiologie et de Pneumologie de Québec-Université Laval, QC, Canada.
Peter G. Middleton, CITRICA, Department of Respiratory & Sleep Medicine, Westmead Hospital and Clinical School University of Sydney, NSW, Australia.
Elias Matouk, Research Institute of the McGill University Health Centre, QC, Canada.
Jean-Marie Houle, Laurent Pharmaceuticals Inc., QC, Canada.
Radu Pislariu, Laurent Pharmaceuticals Inc., QC, Canada.
Patrick Colin, Laurent Pharmaceuticals Inc., QC, Canada.
Irenej Kianicka, Laurent Pharmaceuticals Inc., QC, Canada.
Diane Potvin, Innovaderm Research, QC, Canada.
Danuta Radzioch, Research Institute of the McGill University Health Centre, QC, Canada.
Tom Kotsimbos, The Alfred Hospital, Melbourne VIC, Australia.
Jonathan B. Zuckerman, Maine Medical Center, Portland, ME, USA.
Samya Z. Nasr, University of Michigan Health System, Ann Arbor, MI, USA.
Theodore G. Liou, University of Utah, Salt Lake City, UT, USA.
Larry C. Lands, Research Institute of the McGill University Health Centre, QC, Canada. Electronic address: larry.lands@mcgill.ca.

Abstract

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) 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 points with LAU-7b and 1.95 ppFEV with placebo, a 0.77 ppFEV (40 s) difference, p=0.345, and a 0.95 ppFEV (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV through 24 weeks showed differences of 1.01 and 1.23 ppFEV, 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.