Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study.
BACKGROUND
Kids B-LONG was a multicentre, open-label, phase 3 study assessing the safety, efficacy, and pharmacokinetics of recombinant factor IX Fc fusion protein (rFIXFc) in previously treated paediatric patients younger than 12 years with severe haemophilia B.


METHODS
The study enrolled 30 previously treated boys younger than 12 years with haemophilia B (≤2 IU/dL [≤2%] endogenous coagulation factor IX [FIX] activity). All patients were initially given rFIXFc prophylaxis (50-60 IU/kg) once per week with adjustments to dose (≤100 IU/kg per infusion) or dosing frequency (up to two times per week) as needed. The primary outcome measure was development of inhibitors (neutralising antibodies). Secondary outcomes were pharmacokinetics, annual bleeding rate (ABR), spontaneous joint ABR, the number of infusions and dose required to resolve a bleed, time from last infusion of rFIXFc to a bleeding episode, assessment of response to treatment, and total annualised rFIXFc consumption for prevention and treatment of bleeding episodes. All patients underwent sequential pharmacokinetic evaluations of their prestudy FIX and rFIXFc. The completed trial is registered with ClinicalTrials.gov, number NCT01440946.


RESULTS
No patients developed inhibitors to rFIXFc; in the 30 enrolled patients the most common adverse events were nasopharyngitis (n=7; 23%) and fall (n=6; 20%); four patients (13%) had serious adverse events. Overall, rFIXFc exhibited a prolonged half-life of 68·6 h (95% CI 61·8-76·0), reduced clearance, and similar recovery compared with prestudy FIX. The median ABR was 2·0 (0·0-3·1) overall and 0·0 (0·0-0·0) for spontaneous joint bleeds; ten (33%) of 30 patients reported no bleeding, and 19 (63%) reported no joint bleeding on-study. The median average prophylactic dose of rFIXFc was 58·6 IU/kg (IQR 52·3-64·8) per week. Throughout the study, 29 (97%) of 30 patients remained on once per week infusions.


CONCLUSIONS
Weekly infusions of rFIXFc were well tolerated and resulted in low bleeding rates in children with severe haemophilia B.


BACKGROUND
Biogen, Sobi.
Van Creveldkliniek, University Medical Center Utrecht, Utrecht, Netherlands.
Kathelijn
K
Fischer
Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI, USA.
Roshni
R
Kulkarni
Our Lady's Children's Hospital, Dublin, Ireland.
Beatrice
B
Nolan
Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; National Health Laboratory Service, Johannesburg, South Africa.
Johnny
J
Mahlangu
Basingstoke and North Hampshire Hospital, Basingstoke, UK.
Savita
S
Rangarajan
Biogen, Cambridge, MA, USA.
Giulia
G
Gambino
Biogen, Cambridge, MA, USA.
Lei
L
Diao
Biogen, Cambridge, MA, USA.
Alejandra
A
Ramirez-Santiago
Biogen, Cambridge, MA, USA.
Glenn F
GF
Pierce
Biogen, Cambridge, MA, USA. Electronic address: geoff.a.allen@gmail.com.
Geoffrey
G
Allen
D002648:Child; D002675:Child, Preschool; D005164:Factor IX / Q000627:therapeutic use*; D006395:Hemarthrosis; D002836:Hemophilia B / Q000188:drug therapy*; D006470:Hemorrhage; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000627:therapeutic use*; D008297:Male; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016896:Treatment Outcome
D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; C000599709:factor IX Fc fusion protein; D005164:Factor IX