Alaa Hamed, MD, Global Head of Medical Affairs Rare Diseases at Sanofi, discusses results from the phase 2 ElevAATe clinical trial of efdoralprin alfa in patients with alpha-1 antitrypsin deficiency (AATD).
AATD is an inherited disease that causes an increased risk of having chronic obstructive pulmonary disease (COPD), liver disease, skin problems, and vasculitis. Symptoms may include shortness of breath and wheezing, repeated infections of the lungs and liver, yellow skin, fatigue, rapid heartbeat when standing, vision problems, and weight loss. However, some people with AATD do not have any symptoms. AATD is caused by genetic changes in the SERPINA1 gene, resulting in too little or no working alpha-1 antitrypsin protein (AAT) to be made.
Efdoralprin alfa is a recombinant human AAT-Fc fusion protein, designed to achieve a longer half-life than plasma-derived augmentation therapy, restore and maintain functional AAT levels to the normal range, and inhibit neutrophil elastase and other proteases that can cause lung tissue damage.
The ElevAATe clinical trial (NCT05856331) is a phase 2 double-blind, randomized, active-control, parallel group study evaluating the pharmacokinetics, pharmacodynamics, immunogenicity, and safety of efdoralprin alfa compared to standard of care in adults with AATD emphysema. Results from this study were presented at the 2026 American Thoracic Society (ATS) International Conference.
Efdoralprin alfa, dosed every three weeks, was observed to achieve mean increases in functional alpha-1 antitrypsin (fAAT) trough levels more than three times greater than plasma-derived protein (pdAAT) dosed weekly. All key secondary endpoints in the study were also met. In patients dosed every three weeks, fAAT levels remained above the normal threshold (23.8 μM) for 100% of days during the 32 week study compared to 41% of days in patients on a standard of care augmentation therapy.
Efdoralprin alfa was also well tolerated, with no participants experiencing treatment-emergent adverse events leading to permanent discontinuation of study intervention. The most common adverse events were COPD exacerbations, headache, and COVID-19 infection. The incidence of grade 2 or greater COPD exacerbations, considered an adverse event of special interest in the ElevAATe study, were lower for the efdoralprin alfa every three weeks arm versus the efdoralprin alfa every four weeks and pdAAT arms.
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To learn more about AATD and other rare metabolic disorders, visit https://checkrare.com/diseases/metabolic-disorders/
