Phase 2 data for efdoralprin alfa demonstrate the recombinant protein maintains normal protein levels with less frequent dosing than current standards of care for patients with alpha-1 antitrypsin deficiency (AATD)-related emphysema.
RT’s Three Key Takeaways:
- Superior Protein Restoration: The investigational recombinant protein efdoralprin alfa achieved mean increases in functional protein levels more than three times greater than the current standard-of-care augmentation therapy.
- Extended Maintenance Levels: Patients receiving the therapy every three weeks maintained normal protein levels for 100% of the 32-week study period, compared to 41% of days for those on weekly plasma-derived treatments.
- Reduced Dosing Frequency: The study results suggest the potential for a restorative approach that requires dosing only every three or four weeks while maintaining protective protein levels for patients with emphysema.
Data from the global ElevAATe phase 2 study demonstrated that the investigational therapy efdoralprin alfa is superior to standard-of-care augmentation therapy in achieving and maintaining normalized functional alpha-1 antitrypsin (fAAT) levels in adults with alpha-1 antitrypsin deficiency (AATD)-related emphysema, according to Sanofi.
The results, presented at ATS 2026, showed that efdoralprin alfa dosed every three weeks achieved mean increases in fAAT trough levels more than three times greater than weekly plasma-derived protein (pdAAT). In the group receiving the investigational therapy every three weeks, fAAT levels remained above the normal threshold for 100% of days during the 32-week study, compared to 41% of days for those on standard augmentation therapy.
AATD is a rare genetic condition characterized by low levels or a total absence of AAT, a protein produced by the liver that protects lung tissue from inflammation and damage. Without sufficient fAAT, patients often experience progressive lung tissue deterioration and develop emphysema, a form of chronic obstructive pulmonary disease (COPD).
“AATD presents a persistent clinical challenge. Widespread lack of awareness of the condition as a genetic cause of some forms of COPD leaves many patients underserved. Without treatment to address the underlying AAT protein deficiency, these patients are unable to maintain protective protein levels and become vulnerable to progressive lung disease,” said Igor Barjaktarevic, MD, PhD, associate professor, David Geffen School of Medicine at UCLA, and principal investigator on the ElevAATe phase 2 study, in a news release. “The ElevAATE data suggest efdoralprin alfa, through its mechanism of action, may be able to restore normal AAT levels and keep patients in that range for longer than the standard-of-care therapy, helping to address an unmet need of this disease with a restorative recombinant approach.”
The double-blind, randomized study evaluated 97 patients who received efdoralprin alfa every three or four weeks, or weekly pdAAT. At week 32, the mean change in average serum fAAT trough concentrations for the group receiving the therapy every three weeks was 24.1μM, compared to 7.6μM for the pdAAT group.
Efdoralprin alfa is a recombinant human AAT-Fc fusion protein designed to have a longer half-life than traditional plasma-derived treatments, which have served as the standard-of-care for nearly 40 years.
“The data demonstrate efdoralprin alfa, a restorative recombinant therapy designed to achieve a longer half-life than standard of care augmentation therapy, has the potential to raise and sustain fAAT levels within normal range with less frequent dosing,” said Christopher Corsico, global head of development at Sanofi, in a news release. “This could represent an important advancement in the treatment of AATD-related emphysema, offering patients new hope in a disease state where innovation has been limited over the past 40 years.”
The therapy was well tolerated with a safety profile comparable to pdAAT. No participants experienced treatment-emergent adverse events leading to permanent discontinuation of the study intervention. The most common adverse events included COPD exacerbations, headache, and COVID-19 infection. Notably, the incidence of grade 2 or higher COPD exacerbations was numerically lower in the group receiving efdoralprin alfa every three weeks compared to the other study arms.
Sanofi is currently engaging with global regulatory authorities regarding the next steps for efdoralprin alfa. The therapy has received fast track designation and orphan drug designation in the United States (US) and orphan designation in the European Union (EU). Additional long-term safety and efficacy outcomes are currently being evaluated in an open-label extension study.
