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Alprolix shows promise in treatment of severe pediatric hemophilia B
Recombinant Factor IX Fc fusion protein appeared safe and effective in the prevention and treatment of bleeding events in children with severe hemophilia B, according to results from the multicenter, open-label, phase 3 Kids B-LONG trial.
Recombinant Factor IX Fc fusion protein (Alprolix; Bioverativ, Sobi) is a recombinant clotting factor therapy developed for hemophilia B using Fc fusion technology to prolong circulation in the body. Factor IX is fused to the Fc portion of immunoglobin G subclass 1 to extend the therapy’s half-life.
The B-LONG phase 3 study — designed to evaluate Alprolix in previously treated adults or adolescents aged 12 years or older with hemophilia B — demonstrated improved terminal half-life with administration every 1 to 2 weeks, resulting in low annual bleeding rates.
“The Medical and Scientific Advisory Council of the National Hemophilia Foundation recommends that prophylaxis be considered the optimal treatment regimen for people with severe hemophilia B, and be initiated early based on the body of evidence demonstrating improved long-term clinical outcomes,” study investigator Roshni Kulkarni, MD, professor emerita in the department of pediatrics and human development at Michigan State University, said in a press release.
In this study, researches assessed the safety, efficacy and pharmacokinetics of Alprolix in 30 boys aged younger than 12 years of age (median age, 5 years) with previously treated hemophilia B. All boys received Alprolix prophylaxis (50-60 IU/kg) once per week and could receive adjustments in dose ( 100 IU/kg per infusion) and frequency (up to two times per week) as needed.
“To date, Kids B-LONG is the largest study to evaluate the safety and efficacy of extended half-life Factor IX therapy in children with hemophilia B, and the study’s results align with those in studies of Alprolix in adults and adolescents,” Kulkarni added.
The development of inhibitors served as the primary endpoint. Secondary endpoints included pharmacokinetics, annualized bleeding rate and the number of infusions required to resolve a bleed. All patients underwent sequential pharmacokinetic evaluations of their prestudy Factor IX and recombinant Factor IX Fc fusion protein.
The median average prophylactic dose was 58.6 IU/kg (interquartile range, 52.3-64.8) per week, and 29 (97%) of patients remained on once-weekly infusions.
No patients developed inhibitors to Alprolix. The most common adverse events included nasopharyngitis (23%) and fall (20%). Four patients (13%) experienced severe adverse events.
Of the patients with complete and evaluable pharmacokinetics profiles, Alprolix exhibited a prolonged half-life of 68.6 hours (95% CI, 61.8-76), reduced clearance and similar recovery compared with prestudy Factor IX.
Ten patients reported no bleeding, and 19 patients experienced no joint bleeding events during the study.
Median annual bleeding rate was 2% (95% CI, 0-3.1) overall and 0% for spontaneous joint bleeds.
Sixty bleeding episodes occurred in 20 patients. Most bleeding episodes (92%) were controlled by one or two infusions of Alprolix.
Overall, 22 of 27 patients (80%) received reductions in their dosing frequency with Alprolix compared with prestudy Factor IX. Following a switch to Alprolix therapy, 80% of children extended their dosing interval compared with previous treatment.
The researchers noted further studies are needed to determine whether children with hemophilia B could achieve prolonged dosing intervals with recombinant Factor IX Fc prophylaxis in a real-world setting.
“Pharmacokinetic and efficacy results support the potential for extended interval dosing with recombinant Factor IX Fc compared with standard half-life Factor IX products, with excellent bleeding control,” the researchers wrote. “Furthermore, reduced infusion frequencies associated with efficacy results support the potential for extended interval dosing with recombinant prophylaxis might facilitate increased adoption of and adherence to prophylaxis therapy in pediatric patients with hemophilia B.”
However, well-designed head-to-head studies may better assess the difference in efficacy of recombinant Factor IX Fc compared with recombinant Factor IX, Massimo Morfini, MD, from the Italian Association of Haemophilia Centres (AICE) in Italy, wrote in an accompanying editorial.
“The new recombinant Factor IX Fc protein will allow a better adherence of children and adolescent patients with hemophilia B to prophylaxis,” he added. “The major obstacle to the implementation of prophylaxis in children and adolescents is venous access difficulties. Increasing the interval between venipunctures, for recombinant Factor IX Fc as well as other extended half-life recombinant Factor IX concentrates, will improve patients adherence to therapy.” – by Kristie L. Kahl
Disclosure: Kulkarni reports advisory board roles with Baxter, Bayer, Biogen, BPL, Kedrion, Novo Nordisk and Pfizer; and research funding from Baxter, Biogen and Novo Nordisk. Please see the full study for a list of all other researchers’ relevant financial disclosures. Morfini reports consultant and speakers roles with Bayer, Baxter, Biotest, CSL Behring Symposia, Kedrion, Novo Nordisk, Octapharma, Pfizer and Sobi; and research grants from Baxter, Bayer and Pfizer.