The US Food and Drug Administration (FDA) has approved lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy, for use in adults and children with hemophilia A.
The product is approved for routine prophylaxis to reduce the frequency of bleeding episodes, for on-demand treatment and control of bleeding episodes, and for perioperative management of bleeding.
Lonoctocog alfa is the first and only single-chain product for hemophilia A that is specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing.
The product uses a covalent bond that forms one structural entity, a single polypeptide-chain, to improve the stability of FVIII and provide longer-lasting FVIII activity.
Lonoctocog alfa should be available in the US early this summer, according to CSL Behring, the company developing the drug.
Clinical trials
The approval of lonoctocog alfa is based on results from the AFFINITY clinical development program, which included a trial of children (n=84) and a trial of adolescents and adults (n=175).
Among patients who received lonoctocog alfa prophylactically, the median annualized bleeding rate (ABR) was 1.14 in the adults and adolescents and 3.69 in children younger than 12.
In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.
Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly. Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.
Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).
One patient withdrew from treatment due to hypersensitivity.
None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.
