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

Abstract

Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months' pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 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. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960.

• Authors: Robert Klamroth, Jerzy Windyga, Vlad Radulescu, Peter W Collins, Oleksandra Stasyshyn, Hishamshah Mohd Ibrahim, Werner Engl, Srilatha D Tangada, William Savage, Bruce Ewenstein
• Journal: Blood (Blood) Vol. 137 Issue 13 Pg. 1818-1827 (04 01 2021) ISSN: 1528-0020 [Electronic] United States
• PMID: 33150384 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 by The American Society of Hematology.

Chemical References

• Coagulants
• BAX 855
• Factor VIII

Topics

• Adolescent
• Adult
• Coagulants (adverse effects, pharmacokinetics, therapeutic use)
• Factor VIII (adverse effects, pharmacokinetics, therapeutic use)
• Female
• Hemophilia A (complications, drug therapy)
• Hemorrhage (etiology, prevention & control)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Treatment Outcome
• Young Adult