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

Area of Science:

• Hematology
• Rare Diseases
• Therapeutic Development

Background:

• Congenital factor V (FV) deficiency is a rare bleeding disorder affecting 1 in 1 million globally.
• Current treatment relies on plasma and platelet transfusions, lacking factor-specific replacement therapy.
• Other rare bleeding disorders have approved factor concentrates, highlighting a gap for FV deficiency.

Purpose of the Study:

• To outline a pragmatic pathway for clinical trials of novel factor V (FV) therapies.
• To leverage existing strategies and infrastructure from other rare bleeding disorders (RBDs).
• To advocate for the development of factor-specific replacement therapy for FV deficiency.

Main Methods:

• Reviewing development strategies from other rare bleeding disorders.
• Utilizing existing registry infrastructure and regulatory incentives for rare diseases.
• Proposing phased clinical trials with combined pharmacodynamic and clinical outcome endpoints.

Main Results:

• Two promising therapeutic candidates identified: plasma-derived FV concentrate and engineered activated FV (superFVa).
• In vitro correction of severe deficiency demonstrated by FV concentrate.
• Potent hemostatic activity shown by superFVa in preclinical models.

Conclusions:

• A feasible clinical trial pathway can be established for FV deficiency.
• Phased trials can generate decision-grade evidence for novel FV therapies.
• Modern therapeutic development should be extended to address FV deficiency, a rare bleeding disorder.