Switching from Sucrose-Formulated rFVIII to Octocog Alfa (BAY 81-8973) Prophylaxis Improves Bleed Outcomes in the LEOPOLD Clinical Trials

Abstract

Introduction: 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; octocog alfa; prophylaxis; recombinant proteins.

Conflict of interest statement

G. Kenet: is a member of the Board of Directors/advisory committees and has received consultancy fees from ASC therapeutics, Roche, Sobi, Uniquore, Bayer, Pfizer, BioMarin, Takeda, Roche, Novo Nordisk, Sanofi, PI Healthcare and CSL Behring; has received research funding from BSF, Opko Biologics, Bayer, Pfizer, Roche, Alnylam (Sanofi) and Shire; has received honoraria for participation in speakers’ bureaus from Bayer, BPL, CSL, Roche, Sanofi-Genzyme, Sobi, Spark, Uniquore, Pfizer, Takeda, BioMarin and Novo Nordisk. T. Moulton: is a Bayer employee. B. M. Wicklund: has received consultancy fees from Bayer, Genentech, Novo Nordisk and Shire. S. P. Ahuja: has received consultancy fees from Genentech, Sanofi Genzyme, CSL Behring and XaTek, Inc.; has received patent royalties and research funding from XaTek, Inc. He also has a patent with royalties for ClotChip and a patent for TraumaChek issued to US Patent office. M. Escobar is a member of the advisory boards and/or has received consultancy fees from Biomarin, Novo Nordisk, CSL Behring, Genentech/Roche, Sanofi, Takeda, Pfizer, Bayer, Kedrion, Hemobiologics/LFB, National Hemophilia Foundation, UniQure. J. Mahlangu is a member of the scientific advisory committee of Amgen, Bayer, Baxalta, Biogen, Biotest, CSL Behring, Catalyst Biosciences, Novo Nordisk, Roche and Spark; has received research grants from Bayer, Biogen, BioMarin, CSL Behring, Novartis, Sanofi, Spark, Takeda, Novo Nordisk, Sobi, Roche, Uniqure; has received honoraria for participation in speakers’ bureaus from Alnylam, Bayer, Biogen, Biotest, ISTH, Novo Nordisk, Pfizer, Roche, Sobi, Shire, and World Federation of Hemophilia. The authors report no other conflicts of interest in this work.

© 2023 Kenet et al.

Figures

Figure 1

Patient disposition in the LEOPOLD trials. aDosing regimens for both studies were assigned by the investigator.

Figure 2

Treatment regimen switching from rFVIII-FS to octocog alfa. aData unavailable for previous rFVIII-FS dose; recommended dose for rFVIII-FS prophylaxis is 25 IU/kg 3×W (adults) or 25 IU/kg EOD (children). bThese two patients had an estimated mean dosing frequency prior to the study of 0.39 doses per week and 4.02 doses per week, respectively. cDotted lines represent the overall shift in prophylaxis regimen between pre-study and the start of the respective LEOPOLD studies; bold lines indicate the overall number of patients in each regimen at the start of each LEOPOLD study in relation to the respective previous rFVIII-FS regimens. dPatients were assigned to respective octocog alfa dosing regimens at the investigator’s discretion; the majority of patients remained on their previous dosing interval. eOne patient was represented in more than one previous treatment category.

Figure 3

ABR outcomes by age in patients previously treated with rFVIII-FS who switched to octocog alfa prophylaxis in the LEOPOLD studies. aThe primary efficacy endpoint in the LEOPOLD Kids study was ABR occurring within 48 hours after prophylaxis infusion, selected because of variable treatment intervals in children, for whom a low infusion frequency could also be related to venous access problems.