Results from a large multinational clinical trial (guardian™1) using prophylactic treatment with turoctocog alfa in adolescent and adult patients with severe haemophilia A: safety and efficacy

Abstract

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prophylaxis and treatment of bleeding episodes in patients with severe haemophilia A. This multinational, open-label, non-controlled trial investigated the safety and efficacy of turoctocog alfa, a new rFVIII product. The primary objective was to evaluate safety. A total of 150 patients (24 adolescents and 126 adults) with severe haemophilia A (FVIII activity ≤ 1%), with at least 150 exposure days (EDs) to any FVIII product and no history of inhibitors were enrolled, and 146 patients (97%) completed the trial. All patients received prophylaxis with turoctocog alfa for approximately 6 months and had a mean of 85 EDs during the trial. None of the patients developed FVIII inhibitors, there were no indications of early FVIII inhibitor development and no safety concerns were identified. A total of 225 adverse events were reported in 100 (67%) patients, with the most common being events associated with dosing procedures, headaches, and nasopharyngitis. A total of 499 bleeding episodes were reported during the trial, the majority (89%) were controlled with 1-2 infusions of turoctocog alfa. Based on patient reports, the success rate (defined as 'excellent' or 'good' haemostatic response) for treatment of bleeding episodes was 81%. The overall median annualized bleeding rate was 3.7 (interquartile range: 8.7) bleeds/patient/year. In conclusion, turoctocog alfa provides a new, safe and effective alternative for prophylaxis and treatment of bleeding episodes in patients with haemophilia A.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

“…1 With these dosing instructions, the median dose per injection to treat a bleeding episode was 31.7 IU/kg (range, 6-84), which is in line with doses used with other new rFVIII products; 27.35 IU/kg per dose for efmoroctocog alfa and a mean dose of 45.6 IU/kg for turoctocog alfa was used to stop a bleed. 7,15 The overall median consumption for subjects on rVIII-SingleChain prophylaxis was 4283 IU/kg per year, which is comparable to that of the recently approved long-acting efmoroctocog alfa where a median consumption of 4118.4 IU/kg per year was observed in a study investigating individualized regimens. 21 To our knowledge, this pivotal study accumulated the most EDs for a new rFVIII product, with a total of 14 306 EDs in 174 patients.…”

“…15 Simoctocog alfa (Nuwiq) reported a median ABR of 0.9 in a small study of 32 adult patients; however, this bleeding rate was achieved with a prophylactic regimen requiring dosing every second day. 16 This study was designed to reflect clinical practice and as such, patients were assigned to prophylaxis regimens based on the clinical judgment of the treating physician.…”

“…6,15,17,18 rVIII-SingleChain was also analogous in terms of the numbers of injections needed to achieve hemostatic control; 93.5% of bleeds were controlled with 1 or 2 injections. With 1 or 2 injections, efmoroctocog alfa controlled 97.7% of bleeding episodes, moroctocog alfa (Refacto) controlled 88% (of 677 bleeding events across 2 studies), and rurioctacog alfa pegol (Adynovate) controlled 95.9% of bleeding episodes.…”

Long‐term patterns of safety and efficacy of bleeding prophylaxis with turoctocog alfa (NovoEight®) in previously treated patients with severe haemophilia A: interim results of the guardian™2 extension trial

“…Restoration of haemostasis with FVIII concentrates is the standard therapy. Turoctocog alfa (NovoEight â ; Novo Nordisk A/S, Bagsvaerd, Denmark) is a third generation human recombinant B domain-truncated FVIII molecule [3] that in Phase 3 trials -guardian TM 1 (adolescent and adult patients ≥12 years) [4] and guardian TM 3 (paediatric patients <12 years) [5] -demonstrated favourable efficacy and safety profiles; there were no inhibitors and no safety concerns were observed. Subjects who completed the guardian This letter presents a preplanned interim analysis of data collected up to September 1, 2012 for the guardian TM 2 extension trial.…”

[Use of Kovaltry® in patients with Hemophilia A: clinical and economical aspects from the pivotal clinical trials]

“…mited, efmoroctocog-alfa) [12], NovoEight ® (Novo Nordisk A/S, turoctocog-alfa) [13][14][15], e Nuwiq ® (Octapharma AB, simoctocogalfa) [16]. popolazionE studiata L'efficacia e la sicurezza di Kovaltry ® negli adulti è stata valutata attraverso un programma di sviluppo clinico che comprendeva 2 studi internazionali (Leopold I e Leopold II) [10,11], condotti su oltre 120 adulti trattati in profilassi (età media di circa 30 anni).…”