Real-World Data Support Use of rpFVIII for Acquired Hemophilia A

Wolfgang Miesbach, MD, PhD

Credit: ISTH

A new real-world report supported the use of recombinant porcine factor VIII (rpFVIII; susoctocog alfa) for the treatment of bleeding events in adults with acquired hemophilia A.¹

These data remained in line with previously reported Phase 2/3 findings, reporting no further safety signals and no reported adverse events (AEs) of hypersensitivity reactions or thromboembolic events, known safety concerns with the use of rpFVIII treatment.

“The findings of this study support the use of rpFVIII as first-line treatment for acquired hemophilia A and align with findings from the Phase II/III clinical trial of rpFVIII in the treatment of bleeding events in adults with acquired hemophilia A,” wrote the investigative team, led by Wolfgang Miesbach, MD, PhD, Haemophilia Centre, Medical Clinic 2, University Hospital Frankfurt.

A rare, autoimmune disease, acquired hemophilia A is characterized by inhibitory autoantibodies against endogenous FVIII.² Its treatment is typically based on controlling bleeding and eradicating inhibiting antibodies, but bypassing agents (BPAs) used in treatment often carry a risk of thromboembolic events that can be enhanced by patient comorbidities.³

rpFVIII is indicated for bleeding events in adults with acquired hemophilia A in the European Union, United Kingdom, and United States.⁴ Treatment guidelines for acquired hemophilia A recommend using BPAs or rpFVIII as a first-line therapy, dependent on inhibitor titer, treatment cost, and availability.

In a Phase 2/3, prospective, multicenter, open-label study, rpFVIII, 86% of patients achieved successful cessation of initial bleeding events.⁵ For this EU post-authorization safety study (PASS), Miesbach and colleagues assessed the safety, effectiveness, and utilization of rpFVIII in real-world clinical practice.¹

This PASS was performed between December 2016 and July 2021 at 15 sites in 8 countries—patients were followed for 180 days after the last administration of rpFVIII. In the event of a new or rebleeding event treated with rpFVIII, patients were followed for an additional 180 days.

For the study, the primary objective was to document the safety of patients treated with rpFVIII, as determined by AEs, serious AEs (SAEs), and AEs of special interest (AESIs), including immunogenicity, hypersensitivity reactions, and thromboembolic events. Secondary endpoints involved immunogenicity, rpFVIII hemostatic effectiveness, and rpFVIII utilization.

Overall, 50 patients were enrolled, of which 31 (62%) completed the study. Among those who discontinued, the primary reason for discontinuation was death (n = 11). Among those enrolled, the median follow-up was 178 days and the median first dose was 54.0 U/kg.

A total of 148 AEs were reported in 41 patients, including 46 SAEs. Of the SAEs, 5 were considered probably related to rpFVIII—1 was lack of rpFVIII efficacy and 4 were AESIs, including drug resistance due to FVIII inhibition (n = 1), antibody test positive for anti-rpFVIII inhibitors (n = 1), and de novo anti-pFVIII inhibitors (n = 2).

Most AEs were considered moderate in severity and there were no reports of hypersensitivity reactions, thromboembolic events, or dose dispensing medication errors. More than half of patients received rpFVIII as first-line treatment for initial bleeding events.

Among 50 initial events, 37 (74.0%) resolved after the rpFVIII treatment course, in a median of 8.0 days. Among the resolved cases, 35 resolved after an initial rpFVIII treatment course and 2 after a subsequent rpFVIII treatment course.

In their conclusion, Miesbach and colleagues pointed to trends in bleeding event resolution in these data, suggesting a shorter time from the initial bleed to the first rpFVIII infusion could favor bleed resolution.

“A higher proportion of patients receiving first-line rpFVIII achieved resolution of their initial BE than those receiving second-line therapy, suggesting that first-line rpFVIII is potentially better than second-line therapy for resolving initial bleeding events,” they wrote.

References

1. _{Miesbach W, Curry N, Knöbl P, et al. Real-world use of recombinant porcine sequence factor VIII in the treatment of acquired hemophilia A: EU PASS. Ther Adv Hematol. 2024;15:20406207241260332. Published 2024 Sep 2. doi:10.1177/20406207241260332}
2. _{Franchini M, Mannucci PM. Inhibitors of propagation of coagulation (factors VIII, IX and XI): a review of current therapeutic practice. Br J Clin Pharmacol. 2011;72(4):553-562. doi:10.1111/j.1365-2125.2010.03899.x}
3. _{Meeks SL, Batsuli G. Hemophilia and inhibitors: current treatment options and potential new therapeutic approaches. Hematology Am Soc Hematol Educ Program. 2016;2016(1):657-662. doi:10.1182/asheducation-2016.1.657}
4. _{Tiede A, Collins P, Knoebl P, et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica. 2020;105(7):1791-1801. doi:10.3324/haematol.2019.230771}
5. _{Kruse-Jarres R, St-Louis J, Greist A, et al. Efficacy and safety of OBI-1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A. Haemophilia. 2015;21(2):162-170. doi:10.1111/hae.12627}