American Thoracic Society (ATS) International Conference in Orlando | FL | iPharmaCenter
- Badari Andukuri
- 2 hours ago
- 3 min read
Efdoralprin Alfa Outperforms Standard Augmentation Therapy in Alpha‑1 Antitrypsin Deficiency
Sanofi’s investigational therapy efdoralprin alfa showed superior performance to a commonly used plasma-derived augmentation treatment in a phase 2 trial of adults with alpha‑1 antitrypsin deficiency (AATD)-related emphysema. The global ElevAATe study (NCT05856331) demonstrated that efdoralprin alfa achieved higher and more sustained levels of functional alpha‑1 antitrypsin (fAAT), a key lung‑protective protein that is deficient in people living with AATD.
How much did efdoralprin alfa increase functional AAT levels?
In ElevAATe, efdoralprin alfa was compared head‑to‑head with a standard plasma‑derived AAT (pdAAT) augmentation therapy in adults with AATD‑related emphysema. When given once every three weeks (Q3W), efdoralprin alfa produced mean increases in fAAT trough levels more than three times higher than weekly (Q1W) plasma-dervied protein (pdAAT), meeting the primary endpoint with high statistical significance.
All key secondary endpoints were also achieved, supporting the potential of efdoralprin alfa to maintain fAAT in the normal range with less frequent dosing. Over the 32‑week study, patients on Q3W efdoralprin alfa kept fAAT concentrations above the normal threshold of 23.8 μM for 100% of days, compared with 41% of days among those treated with standard‑of‑care plasma‑derived augmentation therapy.
How was the ElevAATe study designed, and what were the safety findings?
ElevAATe was a double‑blind, randomized phase 2 study in adults with AATD‑related emphysema, designed to formally compare efdoralprin alfa with a standard augmentation therapy. Ninety‑seven patients were randomized in a 2:2:1 ratio to receive efdoralprin alfa every three or four weeks, or plasma‑derived AAT once weekly.
Efdoralprin alfa was generally well tolerated and showed a safety profile comparable to plasma‑derived AAT. No participants experienced treatment‑emergent adverse events that led to permanent discontinuation of study treatment.
What is efdoralprin alfa and its mechanism of action?
Efdoralprin alfa is a recombinant human AAT‑Fc fusion protein in development as a restorative treatment for adults with AATD‑related emphysema, with dosing every three or four weeks. Unlike plasma‑derived AAT, which has been the standard‑of‑care augmentation therapy for nearly 40 years, efdoralprin alfa is engineered for a longer half‑life and less frequent infusions.
The treatment is intended to restore and sustain functional AAT within the normal range and to inhibit neutrophil elastase and other proteases that drive progressive lung tissue damage in AATD. If later‑stage trials confirm these findings, efdoralprin alfa could offer a more convenient alternative to weekly augmentation therapy while maintaining normal fAAT levels.
What is alpha‑1 antitrypsin deficiency and why is there an unmet need?
Alpha‑1 antitrypsin deficiency is a rare inherited disorder in which the liver produces very low levels or almost no alpha‑1 antitrypsin, a protein that protects the lungs from inflammation‑related damage. The resulting lack of AAT leads to progressive destruction of lung tissue and the development of emphysema, a form of chronic obstructive pulmonary disease (COPD) that accounts for most deaths linked to AATD.
AATD can also cause liver disease and, in severe cases, may ultimately require lung transplantation. Plasma‑derived AAT augmentation therapy has been available since 1987, but there have been few new approaches reaching routine clinical use, leaving a significant treatment gap for this underdiagnosed population. An estimated 235,000 people worldwide, including nearly 100,000 in the US, may be living with AATD, and around 90% are thought to remain undiagnosed.
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