Continued benefit demonstrated with BAY 81-8973 prophylaxis in previously treated children with severe haemophilia A: Interim analysis from the LEOPOLD Kids extension study

Abstract

Introduction: BAY 81-8973 (Kovaltry®), a recombinant factor VIII (rFVIII) product, was efficacious and well tolerated in paediatric previously treated patients (PTPs) with severe haemophilia A for ≥50 exposure days (EDs) in the LEOPOLD Kids study. Because long-term prophylaxis (≥100 EDs) can provide substantial patient benefits, FVIII products should demonstrate long-term safety and efficacy.

Aim: To demonstrate long-term (≥100 EDs) efficacy and safety of BAY 81-8973 in paediatric PTPs.

Methods: PTPs aged ≤12 years with severe haemophilia A without inhibitors could continue in the ongoing open-label extension study after completing ≥50 EDs in the LEOPOLD Kids main study. Patients received BAY 81-8973 for prophylaxis (25-50 IU/kg ≥2×/week), bleed treatment, and surgery. Bleeds were documented in electronic patient diaries. Inhibitor development was monitored every 6 months.

Results: At the August 2017 interim data cutoff, 46 patients (median [range] age at enrolment, 6.0 [1.0-11.0] years) had spent a median (range) of 602.5 (148-1069) EDs and 4.6 (1.0-5.9) years in the main plus extension studies. Median (quartile [Q]1; Q3) annualised bleeding rate for bleeds within 48 h after a prophylaxis infusion and total bleeds was 1.0 (0.2; 1.9) and 2.0 (0.4; 3.6), respectively. Most (>94%) bleeds were mild or moderate; 71.8% were treated with ≤1 infusion. BAY 81-8973 was also well tolerated with only one treatment-related adverse event (transient, low-titre inhibitor which did not require treatment adjustment).

Conclusion: BAY 81-8973 was efficacious for prophylaxis and treatment of bleeds during >4.5 years in paediatric PTPs with severe haemophilia A.

Keywords: Clinical trial; Full-length factor VIII; Haemophilia A; Long-term observation; Prophylaxis; Recombinant proteins.

Conflict of interest statement

Declaration of competing interest Gili Kenet: Grant and research support: Alnylam Pharmaceuticals, Bayer, Bio Products Laboratory, Opko Biologics, Pfizer and Shire. Advisory boards, honoraria for consultancy/lectures: Alnylam, Bayer, CSL Behring, Opko Biologics, Pfizer, Shire and Roche. Rolf Ljung: Advisory board or data safety monitoring committees: CSL Behring, Pfizer, Sobi, Shire, Bioverativ (last 5 years) and speaker's fees from Bayer, Shire, Novo Nordisk, Pfizer and Sobi (last 5 years). Luminita Rusen reports no conflict of interest. Bryce Kerlin: has served as an advisory board member for Bayer HealthCare and has received research support from Novo Nordisk A/S and CSL Behring Foundation for Research and Advancement of Patient Health. Victor Blanchette: Member of data safety monitoring boards for Octapharma and Shire. Received fees for participation in advisory boards/education events for Bayer HealthCare, Bioverativ, Novo Nordisk, Roche, Shire and Spark Therapeutics. Recipient of research grants from Bayer HealthCare, Bioverativ and Shire. Sonata Saulytė-Trakymienė: Has received speaker fees from Bayer, Shire and Novo Nordisk over the last 5 years. Valentina Uscatescu reports no conflicts of interest. Horst Beckmann, Despina Tseneklidou-Stoeter, and Nikki Church are employees of Bayer.

Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.