Results observed in healthy subjects suggest ACE910, a factor VIIIa-mimetic bispecific antibody, may be safe and effective for patients with severe hemophilia A.
The data indicate that a weekly injection of ACE910 may prevent excessive bleeding, whereas existing hemophilia treatments require 2 to 3 injections per week.
Furthermore, ACE910 may be less likely to prompt factor VIII inhibitors, and the drug may be effective in patients who already have inhibitors.
Researchers reported the results of this phase 1 trial in Blood.
The team enrolled healthy male volunteers (ages 20 to 44), 40 of whom were Japanese and 24 of whom were Caucasian.
In part A of the study, the Japanese volunteers were randomized to receive 1 of 5 doses of ACE910 (ranging from 0.001 to 1 mg/kg) or placebo subcutaneously. There were 6 subjects per ACE910 dose group and 10 subjects who received placebo.
In part B, the Caucasian volunteers were randomized to receive 1 of 3 doses (ranging from 0.1 to 1 mg/kg) or placebo subcutaneously. There were 6 subjects in each group.
The volunteers were monitored based on their dose group, ranging from 4 weeks of observation for 0.001 mg/kg to 24 weeks for 1 mg/kg.
In all 48, subjects received ACE910. The researchers said that doses up to 1 mg/kg appeared to be safe. There were 15 adverse events (AEs) in 13 (27.1%) subjects receiving ACE910, compared to 6 AEs in 4 (25%) subjects receiving placebo.
There was 1 moderate AE (nasopharyngitis in 1 Caucasian subject receiving ACE910 at 0.1 mg/kg), but all other events were mild. There were no serious AEs or AEs that led to study withdrawal. The incidence of AEs did not differ according to dose or ethnicity.
The researchers did not observe any cases of hypercoagulability, hypersensitivity, serum cytokine concentration abnormality, or injection site reaction.
ACE910 absorbed into the plasma at a steady rate similar for both Japanese and Caucasian volunteers and remained in the blood with a half-life of 4 to 5 weeks, suggesting the drug’s therapeutic effects could be sustained with once-weekly subcutaneous dosing of ACE910.
Two subjects (1 Japanese and 1 Caucasian) were positive for anti-ACE910 antibodies. One subject was positive for antibodies before and after receiving ACE910, and the other was only positive after.
“These data are very encouraging for patients with severe hemophilia A, irrespective of the presence of factor VIII 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 in Kashihara, Japan.
“The first clinical investigation of this drug in hemophilia A patients with or without factor VIII inhibitors has already been implemented, and phase 3 studies are being planned to start in the near future.”
Interim results of a phase 1 study of ACE910 in hemophilia A patients (with and without inhibitors) were presented at ISTH 2015. And ACE910 was recently granted breakthrough designation from the US Food and Drug Administration.
