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Orphan drug development in alpha-1 antitypsin deficiency
Franziska C Trudzinski1, Maria Ada Presotto2, Emanuel Buck2
1Department of Pneumology and Critical Care Medicine, Thoraxklinik, Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), University of Heidelberg, Röntgenstraße 2, 69126, Heidelberg, Germany. franziska.trudzinski@med.uni-heidelberg.de.
Alpha-1 antitrypsin deficiency (AATD) drug development has resulted in one FDA-approved orphan drug. Current research focuses on novel gene therapies and recombinant protein platforms to address unmet needs like AATD-associated liver disease.
Area of Science:
- Biochemistry
- Pharmacology
- Genetics
Background:
- Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder impacting lung and liver health.
- The US Orphan Drug Act aims to incentivize development for rare diseases like AATD.
Purpose of the Study:
- To evaluate the impact of the US Orphan Drug Act on AATD therapeutic development.
- To provide a quantitative analysis of FDA orphan drug approvals and designations for AATD.
Main Methods:
- Cross-sectional analysis of the FDA orphan drug database (data up to July 16, 2021).
- STROBE criteria were adhered to for observational study reporting.
Main Results:
- One compound, alpha-1-proteinase inhibitor (human), received orphan drug approval in 1987.
- Sixteen compounds obtained FDA orphan drug designation, encompassing various therapeutic modalities including protein, anti-inflammatory, mucolytic, gene, and cell therapies.
- AATD drug development mirrors that of other rare conditions, with one approval based on a straightforward technology.
Conclusions:
- The current therapeutic landscape for AATD has one approved orphan drug, with ongoing development focusing on recombinant AAT production and gene therapies.
- Addressing extrapulmonary manifestations, particularly AATD-associated liver disease, remains a significant unmet medical need.
- Innovative approaches like gene therapy offer potential for a more comprehensive treatment strategy for AATD.
