Sanofi's Efdoralprin Alfa Shows Superiority in Emphysema Treatment

Sanofi announced data from the global ElevAATe phase 2 study demonstrated superiority of investigational efdoralprin alfa over standard-of-care therapy in achieving and maintaining normalized functional alpha-1 antitrypsin levels in adult patients with alpha-1 antitrypsin deficiency-related emphysema. These results are being presented at the 2026 American Thoracic Society International Conference in Orlando. Efdoralprin alfa, dosed every three weeks, achieved mean increases in fAAT trough levels more than three times greater than plasma-derived protein dosed weekly, meeting the primary endpoint . All key secondary endpoints in the study were also met, highlighting the potential for efdoralprin alfa to be the first therapy to sustain normal fAAT levels for patients and do so with less frequent dosing. In patients dosed Q3W, fAAT levels remained above the normal threshold for 100% of days during the 32-week study compared to 41% of days in patients on a standard-of-care augmentation therapy. AATD is an underdiagnosed, rare genetic condition that can cause considerable respiratory illness and is characterized by low levels or absence of AAT, a protein designed to protect the lungs from damaging inflammation. Without adequate fAAT levels, patients often experience progressive deterioration of the lung tissue and may develop emphysema, the most common form of chronic obstructive pulmonary disease, accounting for up to 72% of deaths in people with AATD. An estimated 90% of individuals with AATD are believed to be undiagnosed. Efdoralprin alfa was well tolerated with a safety profile comparable to pdAAT, with no participants experiencing treatment-emergent adverse events leading to permanent discontinuation of study intervention. The most common TEAEs in the efdoralprin alfa Q3W, efdoralprin alfa Q4W and pdAAT therapy arms were COPD exacerbations, headache and COVID-19 infection. Notably, the incidence of grade greater than or equal to 2 COPD exacerbations, which were captured as an adverse event of special interest in the ElevAATe study, were numerically lower for the efdoralprin alfa Q3W arm versus the efdoralprin alfa Q4W and pdAAT arms. Efdoralprin alfa anti-drug antibodies were detected in two participants and were transient and non-neutralizing. Sanofi is engaging with global regulatory authorities on the appropriate next steps for efdoralprin alfa.