From Fresh Frozen Plasma to First-in-Human: Bringing Coagulation Factor V Deficiency into Therapeutic Trials.

Congenital factor V (FV) deficiency, affecting approximately 1 in 1 million individuals worldwide, remains among the rare bleeding disorders (RBDs) without a licensed factor-specific replacement therapy. While other RBDs have successfully transitioned from plasma-based treatment to approved factor concentrates-exemplified by factor X deficiency's progression to US Food & Drug Administration (FDA)-approved Coagadex and two FDA-approved concentrates for factor XIII deficiency-FV deficiency treatment has remained unchanged for decades, relying solely on plasma and platelet transfusions. Two promising therapeutic candidates have emerged: a human plasma-derived FV concentrate demonstrating in vitro correction of severe deficiency, and an engineered activated FV (superFVa) showing potent hemostatic activity in preclinical models. This commentary outlines a pragmatic pathway to clinical trials, leveraging proven development strategies from other RBDs, existing registry infrastructure, and regulatory incentives for rare diseases. We propose phased trials combining pharmacodynamic endpoints with clinical outcomes, enabling feasible enrollment while generating decision-grade evidence. The time has come to extend modern therapeutic development to FV deficiency.