Sanofi’s AATD Experimental Drug Outperforms Standard Treatment

Rare Daily Staff

Sanofi reported new data this week suggesting its experimental therapy for a rare genetic lung disease could mark a significant shift in treatment for a condition that has seen little innovation in decades.

The data, presented at the American Thoracic Society International Conference, showed the experimental drug, efdoralprin alfa, outperformed the current standard treatment in patients with alpha-1 antitrypsin deficiency (AATD), a condition that can lead to severe lung damage and emphysema.

In a mid-stage clinical trial involving 97 patients, those receiving efdoralprin alfa every three weeks achieved substantially higher levels of the protective protein alpha-1 antitrypsin compared with patients on weekly standard therapy derived from human plasma. Not only were protein levels higher, but they remained within the normal range for the entire 32-week study period—something current treatments have not consistently achieved.

Alpha-1 antitrypsin deficiency is a rare inherited disorder in which the body does not produce enough of a protein that protects the lungs from inflammation and damage. Without it, lung tissue gradually breaks down, often leading to chronic obstructive pulmonary disease (COPD) and emphysema. The condition is widely underdiagnosed; experts estimate that up to 90 percent of people with AATD do not know they have it, leaving many treated for common lung diseases without addressing the underlying genetic cause.

Efdoralprin alfa is designed to replace the missing protein using a lab-engineered version rather than one derived from donated human plasma. The therapy is fused to an antibody fragment to extend its half-life in the body, allowing for less frequent dosing—every three or four weeks instead of weekly infusions. By maintaining stable, normal levels of the protective protein, the drug aims to prevent ongoing lung damage rather than simply slow it.

The trial met its primary and secondary goals, with patients on the three-week dosing regimen showing more than a threefold increase in protective protein levels compared with standard therapy. Importantly, their protein levels stayed above the threshold considered protective 100 percent of the time, compared with just 41 percent for those on existing treatment. The drug was generally well tolerated, with a safety profile similar to current options.

Current therapies, introduced nearly 40 years ago, require lifelong weekly infusions and do not consistently restore normal protein levels. A longer-acting treatment that more reliably protects the lungs could reduce disease progression and ease the burden of care.

Sanofi says it is now in discussions with regulators about next steps. The drug has already received Orphan Drug and Fast Track designations in the United States, signaling both its potential and the unmet need in this patient population. Longer-term studies are ongoing to better understand its safety and durability.

If confirmed in larger trials, efdoralprin alfa could become the first major advance in AATD treatment in decades.