Bispecific antibody mimicking factor VIII

Area of Science:

• Hematology
• Pharmacology
• Immunology

Background:

• Current Factor VIII (FVIII) replacement therapy for severe hemophilia A presents challenges including burdensome intravenous infusions and difficulties in treating patients with FVIII inhibitors.
• There is a need for novel treatments offering improved hemostatic efficacy, simpler administration, and long-acting effects.

Purpose of the Study:

• To evaluate the safety, efficacy, and pharmacokinetic profile of ACE910, a humanized recombinant bispecific antibody mimicking FVIIIa activity, in patients with severe hemophilia A.

Main Methods:

• A Phase I clinical study involving healthy adults followed by a patient study in Japanese individuals with severe hemophilia A (with or without inhibitors).
• Patients received once-weekly subcutaneous injections of ACE910 at three dose levels for 12 weeks.
• Safety assessments included clinical and laboratory findings; efficacy was measured by annual bleeding rates; pharmacokinetics determined the half-life (t1/2).

Main Results:

• ACE910 demonstrated a favorable safety profile with no significant adverse events.
• The drug exhibited a long half-life (t1/2) of approximately 30 days, indicating sustained activity.
• A dose-dependent reduction in median annual bleeding rates was observed, irrespective of inhibitor status. Bleeding rates decreased with increased ACE910 dosage.

Conclusions:

• ACE910 possesses high subcutaneous bioavailability and a long half-life, enabling convenient once-weekly or less frequent administration.
• The bispecific antibody provides effective prophylactic efficacy against bleeding in severe hemophilia A patients, including those with inhibitors.
• ACE910 represents a promising therapeutic option for hemophilia A, addressing limitations of current FVIII replacement therapies.