Journal of Blood Medicine (Jun 2023)
Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials
Abstract
Gili Kenet,1,2 Thomas Moulton,3 Brian M Wicklund,4 Sanjay P Ahuja,5 Miguel Escobar,6 Johnny Mahlangu7 1National Hemophilia Center, Sheba Medical Center, Tel HaShomer, Israel; 2The Amalia Biron Thrombosis Research Institute, Tel Aviv University, Tel Aviv, Israel; 3Bayer, Whippany, NJ, USA; 4Children’s Mercy-Kansas City, Kansas City, MO, USA; 5Rainbow Babies & Children’s Hospital, Cleveland, OH, USA; 6University of Texas Health Science Center, Houston, TX, USA; 7Hemophilia Comprehensive Care Center, Faculty of Health Sciences, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, and National Health Laboratory Service, Johannesburg, South AfricaCorrespondence: Gili Kenet, Amalia Biron Thrombosis Research Institute, Tel Aviv University, Tel HaShomer, 52621, Israel, Tel +972-3-5307356, Fax +972-3-5351806, Email [email protected]: Previous clinical trials established the efficacy and safety of sucrose-formulated recombinant factor (F) VIII (rFVIII-FS/Kogenate FS®/Helixate FS®) and octocog alfa (BAY 81– 8973/Kovaltry®; LEOPOLD trials).Aim: To report the results of a post hoc subgroup analysis assessing efficacy and safety outcomes in patients with hemophilia A who were receiving rFVIII-FS prior to enrolling into the LEOPOLD I Part B and LEOPOLD Kids Part A clinical trials and switching to octocog alfa.Methods: LEOPOLD I Part B (NCT01029340) and LEOPOLD Kids Part A (NCT01311648) were octocog alfa Phase 3, multinational, open-label studies in patients with severe hemophilia A aged 12– 65 years and ≤ 12 years, respectively. Annualized bleeding rate (ABR) was the efficacy endpoint for both studies. Safety endpoints included adverse events (AEs) and development of FVIII inhibitors.Results: Of the 113 patients in both LEOPOLD trials, 40 (35.4%) patients received rFVIII-FS prophylaxis pre-study and had data available for pre-study total ABR. In LEOPOLD I Part B (n = 22, 35.5%), median (Q1; Q3) total ABR decreased from 2.5 (0.0; 9.0) pre-study to 1.0 (0.0; 6.8), and from 1.0 (0.0; 6.0) pre-study to 0.0 (0.0; 6.02) in LEOPOLD Kids Part A (n = 18, 35.3%). Octocog alfa was well tolerated, and no patients had drug-related serious AEs or inhibitors.Conclusion: Treatment with octocog alfa prophylaxis appeared to have a favorable risk–benefit profile compared with rFVIII-FS and thus could be an effective and improved alternative strategy for individualized treatment for children, adolescent and adult patients with severe hemophilia A currently on rFVIII-FS treatment.Keywords: FVIII, hemophilia A, prophylaxis, recombinant proteins, octocog alfa
