Efdoralprin Alfa Meets All Endpoints in Sanofi’s Phase 2 Study, Paving Way for First Recombinant Therapy in AATD

Efdoralprin Alfa Meets All Endpoints in Sanofi’s Phase 2 Study, Paving Way for First Recombinant Therapy in AATD

(IN BRIEF) Sanofi’s investigational therapy efdoralprin alfa met all primary and key secondary endpoints in the Phase 2 ElevAATe study for alpha-1 antitrypsin deficiency emphysema, demonstrating superior efficacy compared to standard plasma-derived therapy. The results highlight its potential as the first recombinant therapy capable of maintaining normal AAT levels with less frequent dosing. Efdoralprin alfa showed a favorable safety profile and could significantly improve treatment convenience and outcomes for patients with AATD.

(PRESS RELEASE) PARIS, 22-Oct-2025 — /EuropaWire/ — Sanofi has announced that its investigational recombinant therapy efdoralprin alfa (SAR447537) successfully met all primary and key secondary endpoints in the global ElevAATe phase 2 study for alpha-1 antitrypsin deficiency (AATD) emphysema, marking a major step forward in the treatment of this rare, debilitating respiratory condition. The findings demonstrate superiority of efdoralprin alfa over standard plasma-derived augmentation therapy in increasing and maintaining functional alpha-1 antitrypsin (AAT) levels within the normal range, with both three-week (Q3W) and four-week (Q4W) dosing intervals outperforming weekly infusions.

In the randomized, head-to-head trial, efdoralprin alfa achieved a statistically significant greater mean increase in functional AAT trough concentrations at steady state compared to weekly plasma-derived therapy at week 32 (p<0.0001). It also demonstrated superior results for key secondary endpoints, including the average concentration of functional AAT (fAAT) and the percentage of days above the lower limit of normal range, for both dosing regimens.

Efdoralprin alfa was well tolerated, showing an adverse event profile comparable to plasma-derived therapies. Additional long-term safety data will be collected through the ongoing ElevAATe OLE phase 2 extension study (NCT05897424).

“These data demonstrate that efdoralprin alfa achieved consistently higher normal functional AAT levels, with less frequent dosing, compared to a current standard of care,” said Christopher Corsico, Global Head of Development at Sanofi. “This is particularly meaningful as maintaining protective protein levels is the cornerstone of pulmonary management of AATD. The ElevAATe results represent the potential for efdoralprin alfa to be a restorative recombinant therapeutic option, reinforcing our commitment to developing treatments for rare and respiratory diseases with high unmet need.”

Dr. Igor Barjaktarevic, Associate Professor at the David Geffen School of Medicine, UCLA, and primary investigator of the ElevAATe study, added: “Achieving and maintaining normal AAT levels with less frequent dosing and independence from blood donation programs would transform treatment for patients living with AATD. The ElevAATe results are encouraging and could mark a significant step toward addressing this long-standing gap in care.”

Efdoralprin alfa, a recombinant human alpha-1 antitrypsin-Fc fusion protein, is being developed as a restorative therapy designed to normalize and sustain functional AAT levels in patients with AATD emphysema. It has already received Fast Track and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA).

Sanofi plans to present the ElevAATe results at an upcoming medical conference and engage with regulatory authorities to determine next steps in the therapy’s development. If approved, efdoralprin alfa could become the first recombinant AAT replacement therapy offering longer dosing intervals and improved treatment convenience compared to existing plasma-derived options.

About AATD
AATD is a rare, inherited disorder characterized by low levels or absence of AAT, a protein produced by the liver that protects the lungs from inflammation and damage.^1,3 The disease causes progressive deterioration of the tissue of the lungs and liver.^1,4 Without adequate AAT levels, affected individuals often experience lung damage and develop COPD, including emphysema, and in severe forms of the disease, patients can sometimes require lung transplantation. Plasma-derived therapies were introduced in 1987 to treat the condition but since then, no new therapies have been introduced. About 235,000 people worldwide live with AATD, with nearly 100,000 people in the US, but about 90% of individuals with AATD are likely undiagnosed.

About efdoralprin alfa
Efdoralprin alfa (SAR447537, formerly known as INBRX-101) is a recombinant human AAT-Fc fusion protein being investigated as a restorative therapy in adults with AATD emphysema, with Q3W or Q4W dosing. The investigational treatment is being studied to restore functional AAT levels to the normal range and inhibit neutrophil elastase, an enzyme that can cause lung tissue damage in patients with AATD. Efdoralprin alfa was granted fast track designation and orphan drug designation by the FDA for the treatment of AATD emphysema.

About ElevAATe
The ElevAATe phase 2 study was a double-blind, randomized study evaluating efdoralprin alfa versus a standard of care plasma-derived augmentation therapy in patients with AATD emphysema. ​Ninety-seven patients were randomized 2:2:1 to receive efdoralprin alfa every three weeks or every four weeks, or plasma-derived augmentation therapy once weekly. The primary endpoint was the mean change in average fAAT concentrations as measured from baseline to average serum trough fAAT concentrations at steady state in patients treated with efdoralprin alfa Q3W or Q4W compared with weekly plasma-derived augmentation therapy, following a treatment period of up to 32 weeks. Key secondary endpoints included mean change in serum fAAT concentration from baseline to fAAT average concentrations at steady state and percentage of days that steady-state functional AAT levels were above the lower limit of the normal range.

About Sanofi
Sanofi is an R&D driven, AI-powered biopharma company committed to improving people’s lives and delivering compelling growth. We apply our deep understanding of the immune system to invent medicines and vaccines that treat and protect millions of people around the world, with an innovative pipeline that could benefit millions more. Our team is guided by one purpose: we chase the miracles of science to improve people’s lives; this inspires us to drive progress and deliver positive impact for our people and the communities we serve, by addressing the most urgent healthcare, environmental, and societal challenges of our time.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY

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SOURCE: Sanofi