Clinical experience with polyelectrolyte-fractionated porcine factor VIII concentrate in the treatment of hemophiliacs with antibodies to factor VIII

Abstract

Circulating antibodies to factor VIII (anti-VIII, “inhibitors”) occurring in patients with hemophilia neutralize porcine factor VIII less readily than human factor VIII in vitro. Over an 18-mo period, 8 patients with anti-VIII were treated with 45 courses (297 infusions) of polyelectrolyte-fractionated porcine factor VIII concentrate (PE porcine VIII). Where no anti-PE porcine VIII was detectable, mean post- infusion rise in plasma factor VIII was 1.29 U/dl/units infused/kg. Above 13 Old Oxford units of anti-PE porcine VIII and 48 Bethesda units of anti-human VIII, there were no postinfusion rises in plasma factor VIII. Where postinfusion rises were detected, clinical responses were good and conventional methods could be used to guide dosage. Ten percent of infusions were followed by febrile reactions, but these were usually mild and decreased in frequency and severity with increasing exposure. Multiple and prolonged courses of therapy were given to some patients without evidence of loss of clinical or laboratory efficacy. PE porcine VIII could provoke anamnestic rises of anti-VIII in susceptible patients, but appeared to have a lower immunogenic potential than human VIII. PE porcine VIII is a rational and effective therapeutic alternative for patients with anti-VIII, particularly those with intermediate level inhibitors who cannot be managed effectively using human factor VIII.

Efficacy of porcine factor VIII in the management of haemophiliacs with inhibitors

“…Recently a new preparation of porcine factor VIII (Hyate:C) has offered a rational and effective therapeutic approach for patients with anti-V1II:C (Kernoff et al, 1984;Kernoff & Tuddenham, 1981;Costello et al, 1981). Our results are in good agreement with these reports: the clinical efficacy of this preparation has been excellent in every severe bleeding episode we have treated.…”

Porcine factor VIII

“…The first published report of the clinical use of Hyate:C appeared in 1984 and described the successful use of the product in eight patients over an 18-month period [6]. A total of 297 infusions were given for the treatment of 45 distinct bleeding episodes.…”

Recombinant B‐domain‐deleted porcine sequence factor VIII (r‐pFVIII) for the treatment of bleeding in patients with congenital haemophilia A and inhibitors

“…Thirty years of clinical experience with plasmaderived porcine FVIII (Hyate:C) demonstrated low cross-reactivity with human FVIII (hFVIII) inhibitors and established clinical efficacy of porcine FVIII to control bleeding in individuals with HA and inhibitors [9][10][11][12][13][14][15]. OBIZUR (OBI-1/BAX801; Baxalta Inc., Deerfield, IL, USA) is a recombinant B-domain-deleted porcine sequence factor VIII (r-pFVIII), with low cross-reactivity to hFVIII inhibitors.…”