Rurioctocog alfa pegol PK-guided prophylaxis in hemophilia A: Results from the phase 3 PROPEL study

Authors: Klamroth, R., Windyga, J., Radulescu, V., Collins PW., Stasyshyn, O., Ibrahim, HM., Engl, W., Tangada, SD., Savage, W., and Ewenstein, BM.

Publication: Blood; November 2020

Affiliations: Vascular Medicine and Haemostaseology, Vivantes Klinikum im Friedrichshain, Berlin, Germany ; Institute of Haematology and Transfusion Medicine, Warsaw, Poland ; University of Kentucky Medical Center, Lexington, Kentucky, United States ; School of Medicine, Cardiff University, Cardiff, United Kingdom ; SI Institute of Blood Pathology and Transfusion Medicine of NAMS of Ukraine, Lviv, Ukraine ; Hospital Kuala Lumpur, Kuala Lumpur, Malaysia ; Baxalta Innovations GmbH, a Takeda company, Vienna, Colorado, Austria ; Baxalta US Inc., Takeda company, Cambridge, Massachusetts, United States Brigham and Women’s Hospital, Boston, Massachusetts, United States ;Takeda, Brookline, Massachusetts, United States.

Abstract: Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs 1% is efficacious and well-tolerated in people with hemophilia A (PwHA). As some may benefit from higher FVIII troughs, the PROPEL trial compared safety and efficacy of 2 target FVIII trough levels in PwHA with severe disease, aged 12-65 years, annualized bleeding rate 2, and previous FVIII treatment. They were randomized to 12 months’ pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1-3% (reference arm) or 8-12% (elevated arm). Treatment-adjustment period was in the first 6 months. Primary endpoint: proportion of PwHA (full analysis set [FAS]) with zero total bleeds (all bleeds) during second 6 months. Overall, 115 male PwHA were randomized (N=115, FAS; N=95, per-protocol analysis set [PPAS]). In the 1-3% and 8-12% arms, respectively, point estimates (95% CI) of proportions of PwHA with zero total bleeds were 42% (29-55%) and 62% (49-75%) in FAS (P=0.055) and 40% (27-55%) and 67% (52-81%) in PPAS (P=0.015). Dosing frequency and consumption varied widely in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA. Serious AEs occurred in 7/115 (6%) PwHA, including 1 treatment-related serious AE in 8-12% arm (transient anti-FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms, with no new safety signal in the 8-12% arm vs previous studies. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. Trial registration: www.ClinicalTrials.gov (#NCT02585960).