The recombinant factor IX (FIX) product rIX‐FP (albutrepenonacog alfa) can maintain high steady‐state FIX trough levels in both adult and pediatric patients with severe hemophilia B, according to a pharmacokinetic study.
“rIX‐FP is a fusion protein genetically linking recombinant human coagulation FIX with recombinant human albumin and has an extended half‐life compared with standard products, allowing a prolonged dosing interval,” wrote Joan C. Gill, MD, of the Medical College of Wisconsin, Milwaukee, along with her colleagues. The findings of the study were published in Haemophilia.
Safety and efficacy of rIX-FP was previously demonstrated for both adults/adolescents and children in two phase 3 trials. In the current analysis, the researchers evaluated mean steady state and observed trough FIX:C levels during prophylaxis with rIX-FP in the two previous trials and assessed the impact on hemophilia B patients.
The researchers studied 90 patients with severe hemophilia B, which included both adult/adolescent (n = 63) and pediatric (n = 27) patients. The adult/adolescent group was administered 35‐50 IU/kg or 50‐75 IU/kg of rIX‐FP every 7 and 10 or 14 days, respectively, while pediatric participants (younger than 12 years old) were given 35‐50 IU/kg of rIX‐FP every 7 days. Only the 7‐ and 14‐day dosing intervals were included in the analysis.
After analysis, the researchers reported that steady‐state FIX trough levels were higher than 5% across all doses in 96.2% and 97.9% of adult/adolescent and pediatric patients, respectively.
Among adults/adolescents, including all dose levels, the mean FIX:C trough levels were 22.26% for 7-day regimens and 12.48% for 14-day regimens. Among children in the study, the mean steady-state FIX:C trough level was 12.80%.
The team reported that these results, which are consistent with low median annualized bleeding rates observed, indicate that sustaining high FIX trough levels may successfully change a case of severe disease into a mild bleeding phenotype.
The authors acknowledged a key limitation of the study was the unknown effects of rIX‐FP remaining within the extravascular space. Further biodistribution studies are required to fully understand these effects.
“Patients may find that an extended dosing regimen would still provide protection from bleeds but be easier to maintain,” they concluded.
The study was funded by CSL Behring. The authors reported financial disclosures related to Bayer, CSL Behring, Kedrion Biopharma, Novo Nordisk, Pfizer, and others.
SOURCE: Gill JC et al. Haemophilia. 2019 Mar 13. doi: 10.1111/hae.13735.