Pharmacokinetic drug evaluation of albutrepenonacog alfa (CSL654) for the treatment of hemophilia.

INTRODUCTION: Replacement therapy for FVIII/IX in hemophilia A/B is more than 50 years old following the discovery of cryoprecipitate by Judith Pool in 1964. On-demand therapy and prophylaxis to treat or prevent bleedings is very demanding owing to the short half-life (HL) of factor concentrates (no more than 12-14 h for FVIII or 16-18 h for FIX). Patients are very eager to prolong the intervals between bolus. The enhanced HL of long-acting recombinant FIX (rFIX) concentrates seems to fulfill this expectance. Areas covered: Great improvements have been achieved in the bio-engineering of new rFIX concentrates. Production, formulation, pharmacokinetics, pharmacodynamics, efficacy and tolerability of albutrepenonacog alfa (rIX-FP, trade name Idelvion) will be addressed. rIX-FP is produced by expression of genetically linked FIX and albumin in Chinese Hamster Ovary cells. rIX-FP exhibits a long HL, low clearance and small volume of distribution. Expert opinion: There is no doubt that rIX-FP, as well as other long-acting rFIX concentrates, will facilitate and improve the adherence to therapy of younger hemophilia patients, toddlers and children. Efficacy, safety and immunogenicity of rIX-FP must be assessed not only during the regulatory clinical trials but also by post-marketing surveillance.