An analysis suggests that rVIII-SingleChain, a recombinant single-chain factor VIII (FVIII) therapy, remains safe and effective as a long-term prophylaxis option for previously treated patients with hemophilia A. The results of this study were reported in the journal Research & Practice in Thrombosis & Haemostasis.
The study was an open-label, nonrandomized phase 3 extension study (ClinicalTrials.gov Identifier: NCT02172950) evaluating rVIII-SingleChain as a prophylaxis therapy for male patients with hemophilia A. There were multiple primary efficacy end points in this study. These included annualized bleeding rates (ABRs) and annualized spontaneous bleeding rates (AsBRs) during prophylaxis and in on-demand treatment, in addition to other efficacy metrics. Incidence of inhibitor development was the primary safety end point of the study.
This extension study had 3 arms. Arm 1 included previously treated patients who had been participants in the AFFINITY clinical trial program evaluating treatment with rVIII-SingleChain. Arm 2 included previously untreated pediatric patients without exposure to FVIII products, and arm 3 included previously treated patients with exposure to an FVIII product but who had not been enrolled in a study involving rVIII-SingleChain. The reported analysis focused on arms 1 and 3.
This extension study enrolled 222 previously treated patients, 204 of whom had participated in lead-in studies involving rVIII-SingleChain. Patients had a median age of 21 years (range, 2-65), and 67 patients were younger than 12 years of age. Patients had a mean time in the extension study of 31 months (SD, 39.91), and the mean number of exposure days was 341.9 (SD, 135.48).
Use of rVIII-SingleChain for prophylaxis was associated with a median ABR of 1.21 (interquartile range [IQR], 0.33-3.03) and a median AsBR of 0.32 (IQR, 0.00-1.19). In 87.1% of evaluated bleeding events, treatment with rVIII-SingleChain was considered to have excellent or good hemostatic efficacy. Across all evaluated surgeries that occurred in this patient population, rVIII-SingleChain was considered to have excellent or good surgical hemostatic efficacy.
ABRs were typically lower in patients receiving rVIII-SingleChain as prophylaxis, compared with its use in on-demand treatment. For patients below 12 years of age, the median ABR with rVIII-SingleChain as prophylaxis was 1.96, while it was 51.44 for treatment on demand, although only 1 patient in this age group was treated on demand. In patients with 12 or more years of age, the median ABR for prophylaxis was 0.98, and it was 13.26 across 10 patients who were treated on demand.
In terms of safety outcomes, detectable inhibitor development reportedly did not occur in previously treated patients in this analysis. Additionally, anaphylactic reactions and thromboembolic events reportedly did not occur in these patients.
The study investigators considered the results of this extension study to provide further support to the notion that rVIII-SingleChain has a favorable safety profile. “rVIII-SingleChain is also highly efficacious and these data have demonstrated the value of routine prophylaxis as patients are able to maintain low bleed rates during long-term use,” the study investigators wrote in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Mahlangu J, Karim FA, Stasyshyn O, et al. Recombinant single-chain factor VIII in severe hemophilia: long-term safety and efficacy in previously treated patients in the AFFINITY extension study. Res Pract Thromb Haemost. 2022;6(2):e12665. doi:10.1002/rth2.12665