Rurioctocog alfa pegol in previously treated patients with severe hemophilia A: What findings did the long-term continuation study bring?
Rurioctocog alfa pegol (Adynovi) is a recombinant coagulation factor VIII modified by pegylation, which results in an approximately 1.5× prolonged biological half-life compared to standard half-life FVIII. Previous studies have already confirmed the favorable profile of this drug in prophylaxis for patients with hemophilia A. Recently published results of a prospective multicenter continuation study in children and adult patients under 75 years old with severe hemophilia A (baseline FVIII level < 1%) were based on an observation period averaging 2.2 years.
Methodology and course of the study
The study included 216 patients, with an average age of 22.8 years at study entry (standard deviation [SD] 15.7). They were administered rurioctocog alfa pegol 2× weekly, either in a fixed dose (45 ± 5 IU/kg for patients aged ≥ 12 years; 50 ± 10 IU/kg for children under 12 years; a dose adjustment was allowed with a maximum of 80 IU/kg), or using a pharmacokinetic (PK) curve aimed at maintaining trough FVIII levels ≥ 3% and peak levels ≤ 200%.
Patients over 12 years old with a fixed dose, if they did not experience spontaneous bleeding over a 6-month period, could subsequently adjust the medication regimen to every 5th day, and after another 6 months to every 7th day. According to a later protocol adjustment, from 2014 some patients could choose whether they wanted to receive a fixed dose or doses adjusted according to the PK curve.
Results
No patient developed an FVIII inhibitor. The estimated average annual bleed rate (ABR) for spontaneous bleeding was 1.20 (95% confidence interval [CI] 0.92–1.56) for 186 patients receiving a fixed dose 2× weekly and 0.96 (0.54–1.71) for 25 patients with PK-adjusted prophylaxis. Overall hemostatic efficacy was rated as good or excellent in 88.6% of bleeding events.
Before entering this continuation study, a target joint was described in about half of the patients (n = 110), particularly in adult males. At the end of the study, a target joint was recorded in only 14 participants.
Patients reported an improvement in health-related quality of life (HR-QoL) in terms of pain, physical, and mental well-being.
Conclusion
This study offers consistent favorable results regarding the efficacy, safety, and immunogenicity of rurioctocog alfa pegol in patients with severe hemophilia A. No new safety signals or inhibitors were detected. The observed bleeding rate was lower at the end of the study than at its beginning.
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Source: Chowday P., Mullins E. S., Konkle B. A. et al. Long-term safety and efficacy results from the phase 3b, open-label, multicentre continuation study of rurioctocog alfa pegol for prophylaxis in previously treated patients with severe haemophilia A. Haemophilia 2020 Jul; 26 (4): e168–e178, doi: 10.1111/hae.14052.
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