Sanofi's Efdoralprin Alfa Demonstrates Superior Efficacy Over Standard Care in Alpha-1 Antitrypsin Deficiency Phase 2 Trial
核心洞察
Sanofi's investigational efdoralprin alfa (搜索) achieved mean increases in functional alpha-1 antitrypsin (搜索) trough levels more than three times greater than plasma-derived therapy in the ElevAATe phase 2 study.
The recombinant therapy maintained normal functional AAT (搜索) levels for 100% of days during the 32-week study compared to 41% for standard-of-care treatment.
Efdoralprin alfa (搜索) represents the first potential therapy to sustain normal functional AAT (搜索) levels with less frequent dosing, offering hope for patients with this rare genetic condition.
Sanofi's investigational efdoralprin alfa (搜索) demonstrated superior efficacy over standard-of-care plasma-derived therapy in achieving and maintaining normalized functional alpha-1 antitrypsin (搜索) (fAAT (搜索)) levels in patients with alpha-1 antitrypsin deficiency (搜索) (AATD (搜索))-related emphysema (搜索), according to phase 2 data presented at the 2026 American Thoracic Society International Conference.
The global ElevAATe phase 2 study showed that efdoralprin alfa (搜索), dosed every three weeks, achieved mean increases in fAAT (搜索) trough levels more than three times greater than plasma-derived protein (搜索) dosed weekly, meeting the primary endpoint with statistical significance (p<0.0001). All key secondary endpoints were also met (p<0.0001).
Clinical Trial Results
The double-blind, randomized study enrolled 97 patients with AATD (搜索)-related emphysema (搜索), randomized 2:2:1 to receive efdoralprin alfa (搜索) every three or four weeks, or plasma-derived augmentation therapy once weekly. The primary endpoint measured mean change in average serum fAAT (搜索) trough concentrations from baseline to steady state at week 32.
Efdoralprin alfa (搜索) dosed every three weeks achieved a 24.1 μM increase (95% CI: 22.8-25.3 μM), compared to 16.8 μM (95% CI: 15.5-18.1 μM) for the four-week dosing regimen and 7.6 μM (95% CI: 6.0-9.3 μM) for plasma-derived therapy. Both efdoralprin alfa dosing regimens significantly outperformed standard care (p<0.0001).
A key secondary endpoint demonstrated that patients receiving efdoralprin alfa (搜索) every three weeks maintained fAAT (搜索) levels above the normal threshold (23.8 μM) for 100% of days during the 32-week study, compared to 89.3% for four-week dosing and only 40.8% for standard-of-care therapy.
Safety Profile
Efdoralprin alfa (搜索) was well tolerated with a safety profile comparable to plasma-derived therapy. No participants experienced treatment-emergent adverse events leading to permanent discontinuation. The most common adverse events across treatment arms were COPD (搜索) exacerbations, headache, and COVID-19 infection.
Notably, the incidence of grade ≥2 COPD (搜索) exacerbations was numerically lower for the three-week efdoralprin alfa (搜索) arm (26.8%) versus the four-week dosing (42.1%) and plasma-derived therapy (44.4%) arms. Anti-drug antibodies were detected in two participants and were transient and non-neutralizing.
Addressing an Unmet Medical Need
AATD (搜索) is an underdiagnosed, rare genetic condition affecting approximately 235,000 people worldwide, with nearly 100,000 in the United States. The disorder is characterized by low levels or absence of AAT (搜索), a protein that protects the lungs from damaging inflammation. Without adequate fAAT (搜索) levels, patients experience progressive lung tissue deterioration and may develop emphysema (搜索), accounting for up to 72% of deaths in people with AATD. An estimated 90% of individuals with AATD remain undiagnosed.
"AATD (搜索) presents a persistent clinical challenge. Widespread lack of awareness of the condition as a genetic cause of some forms of COPD (搜索) leaves many patients under-served," said Igor Barjaktarevic, MD, PhD, Associate Professor at UCLA's David Geffen School of Medicine and principal investigator on the ElevAATe study. "The ElevAATE data suggest efdoralprin alfa (搜索), through its mechanism of action, may be able to restore normal AAT (搜索) levels and keep patients in that range for longer than the standard-of-care therapy."
Therapeutic Innovation
Efdoralprin alfa (搜索) is a recombinant human AAT (搜索)-Fc fusion protein designed to achieve a longer half-life than plasma-derived augmentation therapy. This represents a significant advancement in AATD (搜索) treatment, as plasma-derived therapies have been the standard of care for nearly 40 years without new treatment approaches becoming available.
"The data demonstrate efdoralprin alfa (搜索) has the potential to raise and sustain fAAT (搜索) levels within normal range with less frequent dosing. This could represent an important advancement in the treatment of AATD (搜索)-related emphysema (搜索), offering patients new hope in a disease state where innovation has been limited over the past 40 years," said Christopher Corsico, Global Head of Development at Sanofi.
Regulatory Status and Next Steps
Efdoralprin alfa (搜索) has received fast track designation and orphan drug designation in the United States and orphan designation in the European Union. Sanofi is engaging with global regulatory authorities on appropriate next steps for the investigational therapy. Additional long-term safety and efficacy outcomes are being evaluated in the ElevAATe OLE phase 2 study.
The therapy is currently in clinical development, and its safety and efficacy have not been evaluated by any regulatory authority.