Randomized controlled trial for emphysema with a selective agonist of the gamma type retinoic acid receptor

Palovarotene is an oral γ-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement.REPAIR, was an investigator-initiated, double-blind, placebo-controlled randomized study to assess the safety and efficacy of 5 mg·day(-1) palovarotene given for one year to 262 patients with severe alpha-1-antitrypsin deficiency and emphysema confirmed by computed tomography. Lung volume adjusted 15th percentile point lung density change from baseline in one year was the primary endpoint, functional endpoints were also regularly assessed.We randomly assigned 133 and 129 patients to placebo or palovarotene, respectively. Both groups were well matched for all baseline characteristics, including respiratory medications. At end of the study, 88% and 85% of patients completed one year of treatment with placebo and palovarotene, respectively. Palovarotene was generally well tolerated. In the study completer's population, the placebo-corrected difference of lung density was -0.45 HU at week 28 (p=0.64) and -0.25 HU at week 52 (p=0.94). A treatment difference in functional parameters of the lung in favor of the drug was observed over time suggesting potential pharmacological effects of palovarotene.Palovarotene 5 mg·day(-1) over one year failed to show a significant benefit on lung density in moderate-to-severe emphysema secondary to severe alpha-1-antitrypsin deficiency.