Recombinant FVIII with extended half life safe, effective for hemophilia A
BAX 855, a pegylated, full-length recombinant Factor VIII, appeared safe and effective for the biweekly prophylactic treatment of patients with hemophilia A, according to the results of a phase 2/phase3 study.
“Patients with hemophilia A who adopt a prophylactic regimen can reduce their bleeding rate, and thus reduce the probability of developing chronic arthropathy, which leads to disability,” Barbara A. Konkle, MD, professor of medicine at Puget Sound Blood Center and University of Washington, and colleagues wrote. “Current management of severe hemophilia A (factor VIII < 1% of normal) includes on-demand treatment for bleeding episodes and prophylaxis.”
The average half-life of Factor VIII (FVIII) products ranges from 10 to 14 hours, requiring infusion of FVIII every other day or every 2 to 3 days. Extending the half-life of recombinant FVIII (rFVIII) products could create additional therapeutic options for patients and allow for a reduction in the frequency of prophylactic infusions.
A phase 1 study compared the safety and efficacy of BAX 855 (Adynovate, Baxalta) — a pegylated, full-length rFVIII product with an extended half-life — to the licensed rFVIII product Advate (Antihemophilic factor [recombinant], Baxalta). In previously treated patients with hemophilia A, BAX 855 produced a 1.4-fold higher mean half-life and a 1.5-fold higher mean residence time than Advate.
Konkle and colleagues conducted a pivotal phase 2/phase 3 multicenter, open-label study to confirm the efficacy of BAX 855. The study included data from 137 patients (median age, 29 years; 100% men) with previously treated hemophilia A.
The researchers assigned patients to twice-weekly prophylaxis (40 to 50 IU/kg; n = 120) or on-demand treatment (10 to 60 IU/kg; n = 17).
A comparison of the annualized bleeding rates (ABRs) between patients receiving prophylactic and on-demand treatment served as the primary endpoint. Secondary endpoints included an evaluation of BAX 855 for the treatment of bleeding episodes, the number of infusions needed to treat bleeding episodes and time interval between bleeding episodes.
Patients in the prophylactic arm demonstrated a 90% reduction in ABR compared with those in the on-demand arm (median ABR, 1.9 vs. 41.5), meeting the study’s primary endpoint.
Further, 39.6% of compliant patients in the prophylactic arm experienced no bleeding episodes. Also, 70.4% of patients treated prophylactically reduced their frequency of dosing from their pre-study prophylactic regimens by 30% or more, or by at least one less prophylactic infusion per week.
Using a 4-point rating scale, BAX 855 effectively treated 95.9% of bleeding episodes with one to two infusions, with 96.1% having excellent or good efficacy ratings.
The researchers did not observe the development of any FVIII inhibitory antibodies or safety signals. Fifty-three percent of patients (n = 73) experienced a combined 171 adverse events, including five serious adverse events; however, no serious adverse events were treatment related.
Six patients reported a total of seven adverse reactions that the researchers judged to be treatment-related. They included diarrhea, nausea, headache and flushing.– by Cameron Kelsall
Disclosure: Baxalta provided funding for the study. The researchers report employment and advisory roles with, research support and honoraria from, and stock ownership in Baxalta. Please see the full study for a list of all other researchers’ relevant financial disclosures.