A retrospective study presented at the Thrombosis and Hemostasis Societies of North America 2016 Summit provided real-world data on recombinant porcine factor VIII (rpFVIII) for patients with acquired hemophilia A that suggests that a lower dose of the drug than previously recommended by the FDA still leads to effective bleeding control.
In the clinical trial that served as the basis for rpFVIII’s approval, a primary major adverse event (AE) was the development of anti-porcine FVIII antibodies. However, the results lack generalizability to the real-world patient population due to very specific eligibility criteria, according to Michael Tarantino, MD, lead author of one of the studies presented at this year’s Summit.
To characterize the real-world experience with rpFVIII, Dr. Tarantino, of the Bleeding & Clotting Disorders Institute in Peoria, Illinois, and colleagues conducted a chart review of seven patients with acquired hemophilia A who received rpFVIII at one of four institutions.
Five of the patients treated with rpFVIII for major bleeding achieved good hemostatic efficacy, meaning they required one or two infusions more than estimated to control a bleeding episode. Bleeding ceased within 24 hours in four patients, while another patient’s bleeding ceased within four days. The majority of patients also had no bleeding recurrences.
Three patients developed anti-porcine antibodies, which resulted in one patient withdrawing from treatment. No other rpFVIII-related AEs were reported.
- four patients survived with inhibitor eradication
- two patients died with inhibitors present
- one patient was discharged and died due to unrelated causes 4.5 months later
Notably, the researchers found that patients benefited from a substantially lower dose of rpFVIII than the recommended U.S. FDA dose (initial dose of 200 U/kg followed by maintenance dosing titrated according to bleeding control and trough FVIII activity levels). In the study by Dr. Tarantino and colleagues, an rpFVIII loading dose of 100 U/kg (n=6) or 200 U/kg (n=1) resulted in increased FVIII activity (from <1–9% to 109–650%, within 0.25–7 hours post-dose) in all but one patient.
Subsequent median doses ranged from 30 U/kg to 200 U/kg and were administered at intervals ranging from six to 48 hours.
“The doses of rpFVIII used were substantially less than in the registration study,” Dr. Tarantino and colleagues concluded. “The ability to titrate rpFVIII dose using FVIII activity was considered advantageous, particularly where this allowed a dose reduction over time.” However, the considerable delay observed in the diagnosis of acquired hemophilia may have affected treatment effectiveness in some cases, thus limiting the efficacy of the study outcomes.
Tarantino M, Cuker A, Hardesty B, et al. Practical clinical experience with recombinant porcine FVIII for acquired hemophilia A. Abstract #44. Presented at the 3rd Annual Summit of the Thrombosis & Hemostasis Societies of North America, April 15, 2016; Chicago, IL.
For another take on this issue, read “Drawing First Blood: Choosing Between Treatment Strategies for Patients With Acquired Hemophilia A” in the October issue. We asked Rebecca Kruse-Jarres, MD, MPH, and ASH Clinical News Associate Editor Alice Ma, MD, to debate the merits of newer FVIII replacement products and standard bypassing agents.