FDA Approves Weekly Factor Therapy for Hemophilia A

— Factor VIII replacement therapy provides protection from bleeds with once-weekly dosing

by Mike Bassett, Staff Writer, �鶹��ý February 23, 2023

FDA APPROVED Altuviiio over a computer rendering of a clot forming on a damaged blood vessel.

The FDA has approved the recombinant antihemophilic factor Fc-VWF-XTEN fusion protein-ehtl (Altuviiio) for the treatment of adults and children with hemophilia A, on Thursday.

The first-in-class factor VIII replacement therapy carries indications for the routine prophylaxis to reduce the frequency of bleeds, for on-demand treatment and control of bleeding episodes, and for the perioperative management of bleeding.

Designed to extend protection from bleeds with once-weekly prophylactic dosing for people with hemophilia A, it is the first factor VIII therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on current factor VIII therapies. The drug's notes that it is not indicated for the treatment of von Willebrand disease.

Approval was based on results from two multicenter, prospective, open-label clinical studies -- one including adults and adolescents 12 years of age and older, and one a pediatric study in children under 12 years of age -- in previously treated patients with severe hemophilia A (<1% endogenous factor VIII activity or a documented genetic mutation consistent with severe hemophilia A).

Results from the phase III XTEND-1 trial, published last month in the New England Journal of Medicine, included 133 adults and adolescents who received once-weekly prophylaxis with the antihemophilic factor at 50 IU/kg for 52 weeks. Recipients achieved a median annualized bleeding rate (ABR) of 0 (interquartile range 0-1.04) and an estimated mean ABR of 0.71 (95% CI 0.52-0.97).

In an analysis involving a subgroup of 78 patients switching from a pre-study standard-care factor VIII prophylaxis regimen to the recombinant factor VIII therapy, the mean ABR dropped from 2.96 to 0.69 -- a reduction of 77%, which showed superiority over pre-study prophylaxis (ABR ratio 0.23, 95% CI 0.13-0.42, P<0.001).

In a smaller group of 26 patients in XTEND-1 who received on-demand treatment with the antihemophilic factor for 26 weeks, followed by once-weekly prophylaxis for 26 weeks, the ABR decreased when patients switched from on-demand treatment to prophylaxis (21.42 versus 0.69).

In the pediatric study, among 23 children with at least 26 weeks of exposure, routine prophylaxis resulted in a mean ABR of 0.5 (95% CI 0.2-1.3) and a median ABR of 0 (95% CI 0-1.3) for treated bleeds. For all bleeds whether treated or not, the mean ABR was 3.6 (95% CI 1.6-8.4) and the median ABR was 0 (95% CI 0-4.5).

The most common adverse reactions reported in clinical trials (greater than >10% of subjects) were headache and arthralgia.

The new therapy is contraindicated in patients who have had severe hypersensitivity reactions. Other warnings and precautions include that neutralizing antibodies to factor VIII have been reported.

Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.