Patients with hemophilia A who switched to rVIII-SingleChain (AFSTYLA®) prophylaxis—a recombinant factor VIII (rFVIII) with increased binding affinity to von Willebrand factor compared with other FVIII products—exhibited excellent bleed control and a reduction in infusion frequency.
The findings, from an interim analysis conducted at French hemophilia treatment centers, were published in the journal Thrombosis and Haemostasis.
In the national, noninterventional, longitudinal, multicenter trial (NCT04675541) cohort study, the researchers sought to obtain real-world data from patients treated with rVIII-SingleChain to confirm the efficacy and safety established in the clinical trial program and perform a pharmacokinetic (PK) analysis. Data were obtained between January 2018 and September 2021.
Primary outcome measures included annualized bleeding rate, annualized spontaneous bleeding rate, frequency of dosing, and consumption. They were collected, wherever possible, both prior to and after switching to rVIII-SingleChain.
The current interim analysis included 58 male patients from 14 centers who were treated with rVIII-SingleChain. The median patient age was aged 29 years (range, 5 to 81 years). Overall, 45 individuals had severe hemophilia A, 8 had moderate hemophilia A, and 5 had mild hemophilia A.
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In all, 19% (11 of 58) of the participants had a history of FVIII inhibitor use, all of whom had tolerized the agent. Prior to initiation of rVIII-SingleChain, 16 of the 58 patients received on-demand treatment with another FVIII product; additionally, 42 of the 58 participants had been treated with prophylaxis. Among these 42 individuals, 36 were treated with another FVIII product and 6 were treated with rVIII-SingleChain as part of the AFFINITY clinical trial program.
A total of 43 patients switched to rVIII-SingleChain prophylaxis either from a prior prophylaxis regimen or from on-demand treatment. The study showed that after switching to rVIII-SingleChain, patients maintained excellent bleed control. Following a switch to rVIII-SingleChain, most of the participants maintained or reduced their regimen.
Of note, a majority of individuals who had been treated more than twice weekly with a standard half-life FVIII were able to decrease both their injection frequency and FVIII consumption with rVIII-SingleChain.
Based on a PK analysis, a lower clearance of rVIII-SingleChain (1.9 dL/hour vs 2.1 dL/hour), as well as a longer half-life than previously reported was revealed in both 28 adolescent/adult patients and 6 pediatric patients (15.5 hours and 11.9 hours, respectively, vs 14.5 hours and 10.3 hours).
According to the investigators, “Real-world evidence from patients with hemophilia A treated with rVIII-SingleChain in France demonstrated excellent bleed control . . . and similar . . . PK parameters compared with extended half-life FVIII products.”
Hemophilia A is an X-linked bleeding disorder that results from a deficiency or absence of functional coagulation FVIII. Between 80% and 85% of individuals with hemophilia have hemophilia A, which has an estimated frequency of 1 in 10,000 births.
Guillet B, Hassoun A, Wibaut B, et al. A French real-world evidence study evaluating the efficacy, safety, and pharmacokinetic parameters of rVIII-singlechain in patients with hemophilia A receiving prophylaxis. Thromb Haemost. Published February 9, 2023. doi:10.1055/s-0043-1761449