Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: post hoc subanalysis of the randomized, phase 3 PROPEL study

Carmen Escuriola-Ettingshausen; Robert Klamroth; Miguel Escobar; Oleksandra Stasyshyn; Srilatha Tangada; Werner Engl; Ivan Honauer; Hye-Youn Lee; Pratima Chowdary; Jerzy Windyga

doi:10.1177/20406207231178596

Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: post hoc subanalysis of the randomized, phase 3 PROPEL study

Ther Adv Hematol. 2023 Jul 15:14:20406207231178596. doi: 10.1177/20406207231178596. eCollection 2023.

Authors

Affiliations

¹ HZRM Hämophilie-Zentrum Rhein Main, Mörfelden-Walldorf, Germany.
² Vivantes Klinikum im Friedrichshain, Berlin, Germany.
³ The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁴ National Academy of Medical Sciences of Ukraine, Lviv, Ukraine.
⁵ Takeda Development Center Americas, Inc., 650 East Kendall Street, Cambridge, MA 02142, USA.
⁶ Baxalta Innovations GmbH, a Takeda Company, Vienna, Austria.
⁷ Takeda Pharmaceuticals International AG, Zurich, Switzerland.
⁸ Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, UK.
⁹ Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.

Abstract

Background: The phase 3, prospective PROPEL study demonstrated that pharmacokinetic (PK)-guided prophylaxis targeting elevated factor VIII (FVIII) troughs in patients with hemophilia A resulted in lower annualized bleeding rates (ABRs) and a higher proportion of patients experiencing zero bleeds in the second 6 months of treatment when targeting a FVIII trough of 8-12% versus 1-3%.

Objective: To investigate the benefit of PK-guided prophylaxis with rurioctocog alfa pegol targeting two FVIII trough levels in specific patient subgroups in a post hoc analysis using data from PROPEL.

Design: This is a post hoc analysis of data from the PROPEL study. The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously.

Methods: This post hoc analysis reports data stratified by FVIII half-life (t_1/2), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry.

Results: Targeting an elevated FVIII trough of 8-12% was associated with higher average FVIII levels over time, regardless of FVIII t_1/2 at baseline. The decrease in total ABR between the 8-12% and 1-3% arms was greatest in patients with a FVIII t_1/2 of 6 to <12 h (0.7 versus 3.5); a higher number of target joints, that is, at least four target joints, at baseline (0.2 versus 1.6); the presence of arthropathy (0.1 versus 1.7); and those previously treated on-demand (0.3 versus 1.8).

Conclusion: These results support the feasibility of targeting elevated FVIII levels using personalized rurioctocog alfa pegol prophylaxis. These benefits may be especially important in patients with a short FVIII t_1/2 and those receiving standard prophylaxis with frequent breakthrough bleeds, arthropathy, and target joints.

Registration: ClinicalTrials.gov Identifier: NCT02585960; https://clinicaltrials.gov/ct2/show/NCT02585960.

Keywords: factor VIII; hemophilia A; pharmacokinetics; precision medicine; prevention and control; therapy.

Associated data

ClinicalTrials.gov/NCT02585960