Sanofi's Efdoralprin Alfa Outperforms Standard of Care in Phase 2 AATD Trial

Sanofi's $1.7 billion investment in the rare disease space has yielded promising results, as its drug candidate efdoralprin alfa demonstrated superiority over the current standard of care in a phase 2 trial for alpha-1 antitrypsin deficiency (AATD) emphysema.

Phase 2 Trial Results

The randomized study compared efdoralprin alfa, an AAT-Fc fusion protein, to CSL Behring's Zemaira in patients with AATD emphysema. At the 32-week mark, efdoralprin alfa showed a statistically significant greater mean increase in functional AAT levels compared to Zemaira, meeting its primary endpoint. The trial also achieved key secondary endpoints related to AAT levels.

Notably, efdoralprin alfa demonstrated efficacy with both three- and four-week dosing regimens, potentially offering a less burdensome treatment schedule compared to Zemaira's weekly administration. Sanofi has not yet released comparative data between the two efdoralprin alfa dosing schedules but stated that the results support either frequency.

Market Implications and Next Steps

If approved, efdoralpin alfa would enter a market currently dominated by plasma-derived therapies from CSL, Grifols, and Takeda. Sanofi's drug represents part of a new wave of next-generation AATD treatments under development, including Grifols' subcutaneous candidate in phase 1/2 and Takeda's RNAi therapy in phase 3.

Sanofi plans to meet with regulators to discuss the next steps for efdoralprin alfa. The phase 2 trial was designed by Inhibrx, the company from which Sanofi acquired the drug candidate, with the intention of generating data to support approval.

Financial Outlook

When Sanofi acquired efdoralprin alfa from Inhibrx in early 2024, Houman Ashrafian, Ph.D., head of R&D at Sanofi, projected a potential launch in 2027 with blockbuster sales potential. This forecast was based on the expectation that existing patients would switch to efdoralprin alfa and that it would become the preferred choice for new patients if approved.

The positive phase 2 results mark a significant step toward realizing these projections, potentially positioning Sanofi as a major player in the AATD treatment landscape.