A prospective registry of European haemophilia B patients receiving nonacog alfa, recombinant human factor IX, for usual use

Abstract

Nonacog alfa, a recombinant factor IX (FIX) used for the treatment of haemophilia B, was approved in Europe in 1998. In accordance with European Medicines Agency requirements, a registry study was conducted from 2002 to 2009. A reformulated iso-osmotic version was approved for European use in 2007. This study was conducted to evaluate the safety of nonacog alfa in a usual care setting, and provide clinical trial and postmarketing surveillance data support. This open-label, non-interventional, prospective observational cohort study (registry) comprised 52 sites in nine European countries. Patients with haemophilia B receiving nonacog alfa in either formulation for prevention or treatment were followed on a usual care schedule. A total of 218 patients were enrolled, of whom 66 (30.3%) were <18 years of age. Haemophilia severity was evenly distributed, with baseline FIX activity of <1%, 1-5% and >5% in 33.3%, 36.6% and 30.1% of patients, respectively. One hundred thirty-eight patients received the original formulation alone; 80 switched to or received only the new formulation. There was a low incidence of events of special interest (ESIs), with less-than-expected therapeutic effect in five patients (2.2%), inhibitor development in two (0.9%), thrombosis in one (0.5%) and allergic events in eight (3.7%). These accounted for the majority of the 15 serious AEs reported in six patients. Six patients discontinued because of AEs, primarily related to hypersensitivity. Nonacog alfa was shown to be safe for the treatment of haemophilia B, with a low incidence of serious AEs and ESIs.

Nonacog alfa

“…Lastly, Study 101039 (N ¼ 218) was a European registry study conducted in nine countries to evaluate the safety of nonacog alfa in a usual care setting, with a focus on events of special interest (e.g. lack of effect, inhibitor development, thrombosis, red blood cell agglutination, allergic events) [33]. Previously treated or untreated patients receiving original or reformulated nonacog alfa, as well as patients with a history of inhibitor development or allergy to FIX products, were included.…”

“…Eight patients in the registry study (Study 101039) reported allergic manifestations, with three patients experiencing events that were considered serious adverse events; one patient had a history of allergy to plasma-derived replacement products and two patients experienced a de-novo allergy to nonacog alfa. Symptoms in all patients resolved after switching to a plasma-derived product [33]. Five previously untreated patients in Study 300 experienced eight potentially allergic events within 48 h of nonacog alfa infusion, two of which were severe [29].…”

“…Inhibitors developed in two patients in the registry study, one a new event in a previously untreated patient and the other a recurrence in a patient with a history of inhibitors to plasma-derived products [33]. Two previously untreated patients in Study 300 developed high-titre inhibitors (>5 Bethesda units/dl) that diminished following discontinuation of nonacog alfa and a switch to recombinant FVIIa [29].…”

“…The registry study included a patient receiving continuous infusion of nonacog alfa for 12 days as surgical prophylaxis (the patient underwent orthopaedic surgery for spinal stenosis) who developed asymptomatic distal deep vein thrombosis that was considered possibly related to nonacog alfa treatment [33]. In a second patient (Study 300), a clot that developed in the intravenous access device was judged unrelated to nonacog alfa [29].…”

Products Used to Treat Hemophilia: Recombinant Products

“…One 71-year-old patient experienced deep venous thrombosis in association with hemostatic therapy after the surgery for spinal stenosis [36]. The registry included PMS data for both the original and reformulated rFIX.…”