Hemophilia A is a rare, chronic, genetic disorder that results in impaired clotting mechanisms due to missing or reduced levels of factor VIII.
People with hemophilia A experience recurrent and extended bleeding episodes that cause pain and irreversible joint damage. Some of these bleeding episodes can be life threatening. There are an estimated 16,000 – 20,000 people in the United States with hemophilia A (and 142,000 world wide).
Several orphan approved drugs are available to treat bleeding episodes and 3 orphan antihemophilic Factor drugs - Advate
- are approved for prophylactic use in patients.
One problem with most of the current Factors that are used for prophylactic is that they still require regular infusions (3-4 times per week). Elocate by SOBI and Biogen, is designed to be administered 2 times per week. At the 58th
Annual ASH Meeting, Young et al report on the long term use of this Eloctate in children with hemophilia A.
Qualified subjects who completed Kids A-LONG clinical trial were allowed participate in the individualized prophylaxis study (IP; 25-80 IU/kg every 2-5 days, or 20-65 IU/kg on Day 1 and 40-65 IU/kg on Day 4 if twice weekly), or the modified prophylaxis (MP; for subjects in whom optimal dosing could not be achieved with IP) treatment groups.
Outcome measures included: incidence of inhibitors (neutralizing antibody value ≥0.6 BU/mL identified and confirmed on 2 separate samples drawn approximately 2 to 4 weeks apart and performed at the central laboratory as measured by the Nijmegen-modified Bethesda assay), adverse events (AEs), annualized bleeding rate (ABR), treatment of acute bleeds, and changes to prophylactic consumption and dosing interval.
61/67 subjects who completed Kids A-LONG enrolled in the prophylaxis study [ASPIRE (<6 y, n = 30; 6 to <12 y, n = 31)].
Median (IQR) cumulative rFVIIIFc exposure days for all subjects who received ≥1 intravenous injection (N = 69) were 190.0 (153.0-208.0) days; the median (interquartile range [IQR]) duration of rFVIIIFc treatment was 1.7 (1.5-2.0) years.
No inhibitors were reported.
The type and incidence of AEs observed were consistent with those expected for a pediatric hemophilia population.
95.7% of subjects reported ≥1 AE on-study; 36/448 were serious and 2/448 were assessed as related to rFVIIIFc treatment by Investigators. 30.4% of subjects experienced ≥1 serious AE; none were assessed by Investigators as related to rFVIIIFc. There were no reports of anaphylaxis or serious hypersensitivity events, and no serious vascular thrombotic events.
Median ABRs for subjects on IP (n = 57) were generally lower with rFVIIIFc compared with prestudy FVIII. In the IP group, the ASPIRE Year 1 and Year 2 median (IQR) spontaneous ABRs were 1.0 (0.0-1.0) and 0.0 (0.0-2.3), respectively, for the <6 y cohort (n = 27), and 0.0 (0.0-1.0) and 0.0 (0.0-0.0), respectively for the 6 to <12 y cohort (n = 30).
Overall, 79.8% and 95.8% of bleeding episodes were controlled with 1 or ≤2 intravenous injections, respectively.
Young G, Liesner R, Pasi KJ, et al. Longitudinal Analysis of Long-Term Safety and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Children with Severe Hemophilia a. Presented at the 58th Annual ASH Meeting & Exposition; San Diego, CA; December 3-6, 2016. Abstract #1414.