Severe Hemophilia Antibody May Enhance Current Treatment

Engineered antibody treatment imitates functioning factor VIII to make blood clot properly.

Patients with hemophilia may soon have an effective new treatment option that requires less frequent injections, a recent study indicates.

A study published online recently in the journal Blood found that an antibody designed to stop excessive bleeding in patients with severe hemophilia A may provide a safe and effective therapy with fewer injections than current treatments.

The current standard-of-care for patients with severe hemophilia A seeks to prevent bleeding episodes by maintaining functioning factor VIII (FVIII) levels via engineered or plasma-derived FVIII, the study noted. This treatment approach requires patients to self-inject these FVIII drugs 2 to 3 times weekly.

Additionally, 20 to 30% severe hemophilia A patients develop antibodies to these treatments called FVIII inhibitors. The engineered antibody treatment, called ACE910, is a bispecific antibody that imitates the function of FVIII to make blood clot properly.

The researchers conducted a phase 1 trial to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of ACE910. As a result of the different molecular structure of FVIII, researchers do not expect ACE910 to become disrupted by FVIII inhibitors.

The trial included 40 Japanese and 24 white healthy male volunteers between the ages of 20 to 44 years to compare the drug activity among these patients.

In one part of the study, the Japanese volunteers were randomized to subcutaneously receive 1 of 5 doses of ACE910 that ranged from 0.001 to 1-mg/kg or placebo. In the other part, the white volunteers were randomized to subcutaneously receive 1 of 3 doses that ranged from 0.1 to 1-mg/kg or placebo.

The enrollees were monitored based on dosage that ranged from 4 weeks of observation for 0.001-mg/kg to 24 weeks for 1-mg/kg.

The doses of ACE910 up to 1-mg/kg were found to be safe with minimal adverse events in both treatment groups and there were no cases of hypercoagulability. ACE910 was observed to absorb into plasma at a rate similar among both treatment groups, remaining in the blood at a half-life of 4 to 5 weeks.

These results indicate the therapeutic effects of ACE910 may be sustainable via once-weekly subcutaneous dosing.

"These data are very encouraging for patients with severe hemophilia A irrespective of the presence of FVIII inhibitors, as ACE910 has the potential to offer the opportunity to live more normal lives without constantly planning around the next injection," said study author Midori Shima, MD, PhD, of Nara Medical University. "The first clinical investigation of this drug in hemophilia A patients with or without FVIII inhibitors has already been implemented, and Phase III studies are being planned to start in the near future."