Recombinant single‐chain factor VIII in severe hemophilia: Long‐term safety and efficacy in previously treated patients in the AFFINITY extension study

Abstract

Background rVIII‐SingleChain is a recombinant single‐chain factor VIII used to treat people with hemophilia A. Objectives The aim of this extension study was to investigate the long‐term safety and efficacy of rVIII‐SingleChain prophylaxis in ≥200 previously treated patients (PTPs) with hemophilia A with ≥100 exposure days (EDs). Methods In total, 222 patients were enrolled, of which 204 rolled over from prior rVIII‐SingleChain studies. The median age was 21 years (range, 2–65 years), including 155 patients ≥12 years and 67 patients <12 years. Patients continued with their previously assigned dose and regimen, or switched at the investigator’s discretion. Patients were treated for a mean duration of 31 months (range, 1–47 months), the mean ED was 342 (standard deviation, 135.5), and 212 (95.5%) patients achieved >100 EDs. When the study ended, most patients were on either a prophylaxis regimen of 34.9 (17–62) IU/kg, 3×/week (N = 88; 39.6%), or 37.2 (13–65) IU/kg, 2×/week regimen (N = 72; 32.4%). Results Hemostatic efficacy was rated excellent or good in 87.1% of assessed bleeds. The median (range) annualized bleeding rate was 1.21 (0.0–42.6), and the annualized spontaneous bleeding rate (AsBR) was 0.32 (0.0–33.0) for prophylaxis regimens. Median AsBR was similar for patients treated 3×/week and 2×/week (0.31 and 0.30, respectively). Surgical hemostatic efficacy was rated excellent or good in 100% of surgeries. No inhibitors, anaphylactic reactions, or thromboembolic events were reported in PTPs. Conclusion These results confirm the safety and efficacy of rVIII‐SingleChain as a long‐term prophylaxis treatment modality for PTPs with severe hemophilia A.

Relationship between factor VIII levels and bleeding for rFVIII‐SingleChain in severe hemophilia A: A repeated time‐to‐event analysis

“…The children received 15–50 IU/kg rFVIII‐SingleChain every second day or two to three times a week, at the investigator's discretion based on historical dosing and PK data 18 . The third clinical trial was a phase III open‐label extension study which included persons with severe hemophilia A of all ages receiving rFVIII‐SingleChain prophylaxis (CSL627_3001) 19 . In this trial, the rFVIII‐SingleChain dose was determined by the investigator based on individual PK characteristics, previous FVIII treatment, and bleeding phenotype.…”

“…18 The third clinical trial was a phase III open-label extension study which included persons with severe hemophilia A of all ages receiving rFVIII-SingleChain prophylaxis (CSL627_3001). 19 In this trial, the rFVIII-SingleChain dose was determined by the investigator based on individual PK characteristics, previous FVIII treatment, and bleeding phenotype. Persons included in multiple clinical studies were linked and analyzed as one person.…”

Shifting Paradigms and Arising Concerns in Severe Hemophilia A Treatment

“…55 The rFVIII-SC also exhibited a good safety profile as no inhibitor development, allergic responses, or thromboembolism were recorded in more than 200 previously treated patients (PTPs) with severe hemophilia A over 100 exposure days. 56 Based on a survey comprising 14 Italian Hemophilia Treatment Centres, changing to Afstyla prophylaxis reduced the dose frequency without increasing the factor amount or affecting clinical efficacy. Both physicians and patients were satisfied and stated that the effectiveness of this treatment positively impacted their life quality.…”