Treatment for Alpha-1 Antitrypsin Deficiency Does Augmentation Therapy Work?

Authors: Brantly, M.

Affiliations: Division of Pulmonary, Critical Care and Sleep Medicine, University of Florida College of Medicine, Gainesville, FL, United States.

Publication: American Journal of Respiratory and Critical Care Medicine. 2023. 208. 948–955.

Abstract: Alpha-1 antitrypsin deficiency (AATD) is a rare inherited cause of chronic obstructive pulmonary disease that affects an estimated 250,000 individuals in Europe and North America. Although alpha-1 antitrypsin (AAT) augmentation therapy for individuals with AATD has been available since the late 1980s, about 35 years, this therapy has not been uniformly adopted by many countries. Despite the overwhelming logic that replacement of a missing protein would prevent further loss of lung tissue in individuals with AATD, many regulators remain unconvinced of the clinical utility of AAT augmentation therapy in individuals with AATD because clinical trials to date have not met regulatory designated clinical endpoints. The reason clinical trials have not met mandated clinical endpoints is complex and illustrates the challenges of proving that therapies are effective in rare diseases in general.