Written By: Sheetal Barbade BPharm
Reviewed By: Pharmacally Editorial Team
On October 22, 2025, Sanofi announced positive topline results from the global ElevAATe Phase 2 clinical trial evaluating its investigational drug Efdoralprin alfa in adults with alpha-1 antitrypsin deficiency (AATD) emphysema. The study demonstrated that Efdoralprin alfa met all primary and key secondary endpoints, showing statistically significant superiority in increasing and maintaining functional alpha-1 antitrypsin (AAT) levels compared to the current weekly plasma-derived standard of care. Sanofi, a leading global biopharmaceutical company, is the developer of Efdoralprin alfa, which was acquired from Inhibrx in 2024 and currently holds FDA fast track and orphan drug designations for this indication.
About Efdoralprin
Sanofi’s Efdoralprin alfa (SAR447537, formerly INBRX-101) is a novel recombinant human alpha-1 antitrypsin (AAT)-Fc fusion protein developed specifically for the treatment of alpha-1 antitrypsin deficiency (AATD) emphysema. The drug was originally discovered and developed by Inhibrx, a biotechnology company, as INBRX-101. Sanofi acquired Inhibrx in May 2024 thereby gaining full rights to Efdoralprin alfa.
Efdoralprin alfa represents a first-in-class restorative therapy designed to normalize and sustain functional AAT levels in patients with AATD. Unlike plasma-derived AAT therapies, which are extracted from human donors and require weekly intravenous infusions, Efdoralprin alfa is produced recombinantly using advanced biotechnology, eliminating dependence on plasma supply and enabling longer dosing intervals. The molecule is engineered as a fusion protein containing two AAT molecules linked to an Fc domain, which has been optimized to extend its half-life and achieve higher serum concentrations of functional AAT compared to standard plasma-derived therapy.
The drug works by inhibiting neutrophil elastase, an enzyme that causes lung tissue damage in individuals deficient in AAT. By blocking neutrophil elastase activity, Efdoralprin alfa provides a restorative therapy that protects lung tissue from progressive emphysema damage.
Alpha-1 Antitrypsin Deficiency Emphysema
Alpha-1 antitrypsin deficiency is a hereditary genetic disorder characterized by insufficient levels of alpha-1 antitrypsin, a protein produced in the liver that protects the lungs. Deficiency leads to unopposed activity of proteolytic enzymes such as neutrophil elastase, resulting in progressive destruction of alveolar walls and development of emphysema. AATD emphysema exhibits as difficulty breathing, chronic cough, reduced exercise tolerance, lung hyperinflation, and increased susceptibility to respiratory infections. The disease often presents earlier than typical chronic obstructive pulmonary disease (COPD), frequently diagnosed between ages 25 to 50.
Pivotal Clinical Trial Design and Key Efficacy Results
Study Design and Endpoints
The ElevAATe Phase 2 clinical trial (NCT05856331) was a rigorous, global, randomized, double-blind study designed to evaluate the efficacy and safety of Sanofi’s investigational drug Efdoralprin alfa versus the current standard of care plasma-derived augmentation therapy in adults with alpha-1 antitrypsin deficiency (AATD) emphysema. In this trial, 97 patients were randomized in a 2:2:1 ratio to receive either Efdoralprin alfa every three weeks (Q3W), every four weeks (Q4W), or plasma-derived augmentation therapy weekly. The primary endpoint of the trial is mean change from baseline in functional alpha-1 antitrypsin (fAAT) trough concentrations at steady state after 32 weeks of treatment. Key secondary endpoints assessed the mean change in average serum fAAT concentration at steady state and the percentage of days during which serum fAAT levels remained above the lower limit of normal, providing comprehensive measures of biochemical efficacy and therapeutic coverage.
Efdoralprin alfa demonstrated statistically significant superiority over plasma-derived therapy across the primary and all key secondary endpoints. At week 32, both Q3W and Q4W dosing regimens produced a greater mean increase in functional AAT trough concentrations within the normal physiological range compared to weekly plasma therapy, with a p-value less than 0.0001 indicating high statistical confidence. The drug also achieved superior mean average fAAT concentrations and a higher proportion of days with functional AAT levels above the protective threshold, suggesting sustained biochemical efficacy despite less frequent administration. This represents a significant clinical advance by offering durable therapeutic coverage with reduced infusion frequency, which could translate to improved patient convenience and adherence in real-world settings. These robust efficacy results, coupled with a safety profile comparable to the standard therapy, underscore Efdoralprin alfa’s potential as a transformative recombinant restorative treatment for AATD emphysema
Safety and Adverse Event Profile
Efdoralprin alfa was well tolerated in the Phase 2 study, exhibiting an adverse event profile comparable to the standard plasma-derived therapy. No new safety signals were identified. Sanofi is continuing to collect additional safety data in an ongoing open-label extension study to further characterize the long-term safety profile of Efdoralprin alfa.
Key Opinions
Christopher Corsico, Global Head of Development at Sanofi, highlighted that sustaining normal AAT protein levels is fundamental to managing AATD emphysema, and Efdoralprin alfa’s results illustrate its potential to become the first restorative recombinant therapy for this community, aligning with Sanofi’s commitment to rare and respiratory diseases with unmet needs.
Dr. Igor Barjaktarevic, primary investigator and Associate Professor at UCLA, noted the challenges of treating this debilitating condition and acknowledged that current treatments do not maintain normal AAT levels between infusions. He expressed optimism that Efdoralprin alfa, with its less frequent dosing and independence from plasma donation, could substantially improve treatment experience and patient outcomes for people living with AATD. Together, these expert perspectives underscore the importance of Efdoralprin alfa as a promising new therapeutic option that addresses critical gaps in the care of AATD emphysema patients.
Public Health Implications and Future Treatment Landscape
Efdoralprin alfa’s success marks a significant advancement in managing alpha-1 antitrypsin deficiency emphysema, a rare and underdiagnosed genetic disorder. By providing a recombinant therapy that not only normalizes but maintains functional AAT levels with less frequent dosing, Efdoralprin alfa has the potential to improve disease control, reduce morbidity, and enhance patient quality of life. This innovation could transform the treatment landscape by offering an alternative to plasma-derived augmentation therapies, which require more frequent administration and are limited by plasma supply. Sanofi is actively advancing the clinical development of efdoralprin alfa by assessing its long-term safety and efficacy in ongoing studies, including the ElevAATe Open-Label Extension (OLE) trial (clinical study identifier: NCT05897424). This extension study seeks to provide comprehensive data on durability of therapeutic effect, lung function preservation, and immunogenicity over extended treatment periods.
References
Press Release: Sanofi’s efdoralprin alfa met all primary and key secondary endpoints in alpha-1 antitrypsin deficiency emphysema phase 2 study, 22 October 2025, Sanofi, https://www.sanofi.com/en/media-room/press-releases/2025/2025-10-22-05-00-00-3170787
Study of SAR447537 (INBRX-101) Compared to Plasma-derived A1PI Therapy in Adults with AATD Emphysema (ELEVAATE), ClinicalTrials.gov ID NCT05856331, https://clinicaltrials.gov/study/NCT05856331
Investigation of an Investigational Medication for Alpha-1 Antitrypsin Deficiency (AATD) Emphysema, Sanofi Studies, https://www.sanofistudies.com/us/en/listing/312937/study-of-inbrx-101-compared/