Adynovate demonstrates favorable outcomes in the treatment of hemophilia A

SAN DIEGO — Antihemophilic factor (recombinant), PEGylated, appears to be effective for the prevention and treatment of bleeding episodes among pediatric patients with severe hemophilia A, according to study results presented at the ASH Annual Meeting and Exposition.

“To avoid the sequelae of hemarthroses (eg, target joints and arthropathy), timing Factor VIII infusions to cover periods of physical activity and adherence to a prophylactic schedule are particularly important in children with [hemophilia A],” the researchers wrote. “BAX 8551, a PEGylated, extended half-life, full-length, recombinant Factor VIII built on Advate, was developed to reduce infusion frequency while maintaining or improving therapeutic efficacy.”

Eric S. Mullins, MD, of the Cancer and Blood Diseases Institute at Cincinnati Children's Hospital Medical Center, and colleagues analyzed the efficacy of twice-weekly prophylaxis with BAX 855 (Adynovate, Baxalta) among previously treated pediatric patients with severe hemophilia A. The phase 3, prospective, uncontrolled, multicenter study enrolled children with a Factor VIII (FVIII) level of less than 1% who did not have inhibitors (< 0.6 BU using the Nijmegen modification).

The researchers assessed annualized bleeding rates and the efficacy of bleed treatment using time of the day (morning, 04:00-11:59; afternoon, 12:00-17:59; and evening, 18:00-03:59) and time of the week (weekdays, Monday-Friday; weekends, Saturday-Sunday).

The study included 66 patients; 32 were less than 6 years of age and 34 were between 6 and 12 years of age. Participants were treated with a mean prophylactic BAX 855 dose of 51.1 IU/kg (standard deviation [SD], 5.5) at a mean frequency of 1.8 (SD, 0.2) infusions per week for a mean 48.5 (SD, 7.7) exposure days.

Annualized bleeding rates were highest in the evening [point estimates of the mean, 1.0 (95% CI, 0.7-1.5)] compared with the afternoon (0.6; 95% CI, 0.4-1.0) and the morning (0.5; 95% CI, 0.3-1.1). The point estimate of the mean annualized bleeding rate was higher for weekdays (2.4; 95% CI, 1.7-3.5) compared with weekends (0.9; 95% CI, 0.6-1.2). Annualized bleeding rates were higher in the older patient population for all periods evaluated except mornings.

Seventy minor or moderate bleeding events were reported in 34 participants (51.5%). These patients were treated with a mean BAX 855 dose of 57.9 IU/kg (SD, 31.0). Most bleeds that were treated happened in the evening (n = 24 of 70; 34.3%); fewer bleeds were treated in the morning (n = 10; 14.3%) and in the afternoon (n = 16; 22.9%).

The number of moderate bleeds increased throughout the day, from 2 of 10 (20%) in the morning to 5 of 16 (31.3%) in the afternoon and 17 of 24 (70.8%) in the evening. For 20 of 70 bleeds (28.6%) that were treated, the time of day at which they occurred was unknown.

The mean time between the preceding prophylactic infusion and the bleeding event was comparable for all times of day, ranging from 51 to 54.6 hours (median, 51.4 to 57.8 hours). Less time passed between prophylactic dose and bleeding event on the weekends (38.8 hours; median, 35.7 hours) compared with weekdays (54.6 hours; median, 52.9 hours), suggesting that “the time of infusion was chosen to cover for weekend activities,” according to the study results. Bleeding severity was comparable between weekdays and weekends.

Regardless of the point in time (time of day/period of the week) in which they occurred, 85% or more of the bleeds were treated with 1 or 2 infusions of BAX855. Treatment with the agent was deemed excellent or good for 85% or more of bleeds.

“BAX 855 was shown to be effective for the prevention and treatment of bleeding in this patient population,” the researchers wrote. – by Julia Ernst, MS

Reference:

Mullins ES, et al. Abstract 1409. Presented at: ASH Annual Meeting and Exposition; Dec. 3-6, 2016; San Diego.

Disclosures: Mullins reports receiving from Baxalta, a wholly owned, indirect subsidiary of Shire, and board of directors’ or advisory committee roles with U.S. WorldMeds. Please see the full study for a list of all other researchers’ relevant financial disclosures.