Extended half-life recombinant factor VIII Fc fusion protein (rFVIIIFc) is well tolerated and effective as prophylaxis and for the treatment of bleeds in children with hemophilia A who were previously untreated, according to the final results of a phase 3 clinical trial.

The open-label, multicenter study, PUPs A-LONG, evaluated the safety and efficacy of the treatment in 108 male patients aged less than 6 years at 71 locations across the world. The majority (78%) of participants were aged less than 1 year at the start of the study. Around one-fifth (19%) had a family history of inhibitors, and most of them (80%) had high-risk F8 mutations.

The primary outcome measure of the trial was the percentage of patients with confirmed inhibitor development as measured by the Nijmegen-Modified Bethesda Assay. Secondary outcome measures included the annualized bleeding rate and the number and average dose of rFVIIIFc injections.


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The results of the trial showed that the incidence of inhibitors was 31.1% in patients with 10 or more exposure days. The incidence of high-titer inhibitors was 15.6%, and the median time to high-titer inhibitor development was 9 exposure days. The authors said that the overall inhibitor development was within the expected range and that the development of high-titer inhibitors was on the low end of the range reported in the literature. 

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In terms of safety and tolerability, less than a third (27%) of participants had treatment-related adverse events, the most common being the development of inhibitors. 

The overall median annualized bleeding rate was 1.49 for patients on variable prophylactic dosing regimens.

rFVIIIFc, sold under the brand name Eloctate®, is made of a single molecule of recombinant factor VIII fused to the Fc domain of human immunoglobulin G1. This enables recycling through the neonatal Fc receptor, thereby prolonging the half-life of the treatment.

The study results were published in the journal Blood

References

Königs C, Ozelo MC, Dunn A, et al. First study of extended half-life rFVIIIFc in previously untreated patients with hemophilia A: PUPs A-LONG final results. Blood. Published online April 12, 2022. doi:10.1182/blood.2021013563

An open label study to determine the safety and efficacy of replacement factor VIII protein (known as rFVIIIFc) in previously untreated males with severe hemophilia A. ClinicalTrials.gov. September 9, 2014. Updated April 11, 2022. Accessed April 27, 2022.