ISTH Congress Abstracts

Official abstracts site for the ISTH Congress

MENU 
  • Home
  • Congress Archive
    • ISTH 2022 Congress
    • ISTH 2021 Congress
    • ISTH 2020 Congress
  • Resources
  • Search

Looking Beyond Fixed-Dose Rurioctocog Alfa Pegol Prophylaxis: Post Hoc Analysis of PK-guided Regimens from the PROPEL Phase 3 Study

C. Escuriola-Ettingshausen1, M. Escobar2, J. Windyga3, B. Zulfikar4, S.D. Tangada5, W. Engl6, I. Honauer7, H.-Y. Lee7, R. Klamroth8

1Hämophilie-Zentrum Rhein Main, Mörfelden-Walldorf, Germany, 2University of Texas Health Science Center at Houston, Houston, United States, 3Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland, 4Department of Pediatric Hematology, Istanbul University Oncology Institute, Istanbul, Turkey, 5Baxalta US Inc., a Takeda Company, Cambridge, United States, 6Baxalta Innovations GmbH, a Takeda Company, Vienna, Austria, 7Baxalta GmbH, a Takeda Company, Zürich, Switzerland, 8Department for Internal Medicine, Vascular Medicine and Haemostaseology, Vivantes Klinikum im Friedrichshain, Berlin, Germany

Abstract Number: PB0542

Meeting: ISTH 2021 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: PROPEL primary data showed that targeting 8-12% factor VIII (FVIII) troughs results in fewer bleeds vs 1-3% troughs, which suggests personalized dosing can help control/prevent bleeding in patients without compromising the efficacy/safety of rurioctocog alfa pegol (TAK-660, BAX 855).

Aims: To explore the impact of pre-study treatment regimen (on-demand FVIII [OD] or prophylactic FVIII [PPx]) and annualized bleeding rate (ABR) on the efficacy of TAK-660 prophylaxis targeting 1-3% or 8-12% FVIII troughs.

Methods: Design, primary outcomes, and overall safety of PROPEL (NCT0285960) were previously reported; ethics committee approvals and patient informed consent were obtained. Patients aged 12-65 years with ABR ≥2 were randomized to 12 months’ pharmacokinetic (PK)-guided prophylaxis targeting 1-3% or 8-12% FVIII troughs (first 6 months: treatment adjustment). Subgroups analyzed: patients on previous OD, PPx with average ABR <5 before study start, and PPx with ABR ≥5 before study start. Outcomes in second 6 months: point estimates (95% CI) of mean for ABR and proportion of patients with zero ABR (total [all bleeds], spontaneous, spontaneous joint, injury related).

Results: In the 8-12% arm, total, spontaneous, and spontaneous joint ABRs were lower in all subgroups versus the 1-3% arm (Table 1). Injury-related ABR was lower in the 8-12% arm among previous OD patients and patients on previous PPx with ABR <5, but similar between arms in patients on previous PPx with ABR ≥5. In the 8-12% arm, the proportion of patients with zero total ABR was higher versus the 1-3% arm, regardless of pre-study regimen or ABR (Table 2).

Parameter

On-demand FVIII treatment before study (OD) Prophylactic FVIII treatment before study (PPx)
FVIII trough
level 1-3%
FVIII trough
level 8-12%
Average ABR <5 in 12 months before enrollment Average ABR ≥5 in 12 months before enrollment
FVIII trough
level 1-3%
FVIII trough
level 8-12%
FVIII trough
level 1-3%
FVIII trough
level 8-12%
Patients, n 13 13 19 14 20 16
Total ABR 1.8 (1.0-3.3) 0.3 (0.1-1.2) 2.3 (1.4-3.8) 0.5 (0.2-1.5) 3.5 (2.2-5.5) 2.3 (1.3-4.2)
Spontaneous ABR 0.8 (0.3-1.9) 0.1 (0.0-1.0) 1.7 (0.8-3.3) 0.3 (0.1-1.2) 2.1 (1.1-4.2) 1.1 (0.4-2.6)
Spontaneous joint ABR 0.8 (0.3-2.0) 0.0 1.1 (0.5-2.2) 0.1 (0.0-1.0) 1.4 (0.6-3.4) 0.9 (0.3-2.6)
Injury-related ABR 0.9 (0.3-2.4) 0.2 (0.0-1.2) 0.5 (0.2-1.2) 0.2 (0.0-0.9) 1.3 (0.6-2.6) 1.2 (0.5-2.8)‡
ABR, annualized bleeding rate; CI, confidence interval; FVIII, factor VIII; PPAS, per-protocol analysis set.
*Point estimates and 95% CIs were obtained from a generalized linear model fitting a negative binomial distribution. 
†Patients in the PPAS completed the second 6 months of prophylaxis with no significant protocol deviations. 
‡ One patient experienced 5 knee-related injuries in 6 months that contributed to the injury-related ABR in this subgroup.

Point estimate (95% CI)* of mean for ABR in second 6 months stratified by pre-enrollment regimen and ABR (PPAS†). 

Parameter

On-demand FVIII treatment before study (OD) Prophylactic FVIII treatment before study (PPx)
FVIII trough
level 1-3%
FVIII trough
level 8-12%
Average ABR <5 in 12 months before enrollment Average ABR ≥5 in 12 months before enrollment
FVIII trough
level 1-3%
FVIII trough
level 8-12%
FVIII trough
level 1-3%
FVIII trough
level 8-12%
Patients, n 13 13 19 14 20 16
Patients with total ABR=0, % 46.2
(19.2-74.9)
84.6
(54.6-98.1)
42.1
(20.3-66.5)
71.4
(41.9-91.6)
35.0
(15.4-59.2)
50.0
(24.7-75.3)
Patients with spontaneous
ABR=0, %
69.2
(38.6-90.9)
92.3
(64.0-99.8)
57.9
(33.5-79.7)
85.7
(57.2-98.2)
55.0
(31.5-76.9)
68.8
(41.3-89.0)
Patients with spontaneous joint ABR=0, % 69.2
(38.6-90.9)
100.0
(NA)
63.2
(38.4-83.7)
92.9
(66.1-99.8)
65.0
(40.8-84.6)
81.3
(54.4-96.0)
Patients with injury-related ABR=0, % 69.2
(38.6-90.9)
92.3
(64.0-99.8)
73.7
(48.8-90.9)
85.7
(57.2-98.2)
65.0
(40.8-84.6)
56.3
(29.9-80.2)
ABR, annualized bleeding rate; CI, confidence interval; FVIII, factor VIII; NA, not applicable; PPAS, per-protocol analysis set.
*Patients in the PPAS completed the second 6 months of prophylaxis with no significant protocol deviations. 

Point estimate (95% CI) of proportion of patients with zero bleeds in second 6 months stratified by pre-enrollment regimen and ABR (PPAS*).

Conclusions: Irrespective of pre-study regimen/ABR, targeting 8-12% FVIII troughs lowered bleeding rates. In patients on pre-study PPx with ABR ≥5, 50% and 35% in the 8-12% and 1-3% arms, respectively, achieved zero total bleeds. Across all pre-study PPx patients, 81-93% and 63-65% in the 8-12% and 1-3% arms, respectively, achieved zero spontaneous joint bleeds.

To cite this abstract in AMA style:

Escuriola-Ettingshausen C, Escobar M, Windyga J, Zulfikar B, Tangada SD, Engl W, Honauer I, Lee H-, Klamroth R. Looking Beyond Fixed-Dose Rurioctocog Alfa Pegol Prophylaxis: Post Hoc Analysis of PK-guided Regimens from the PROPEL Phase 3 Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/looking-beyond-fixed-dose-rurioctocog-alfa-pegol-prophylaxis-post-hoc-analysis-of-pk-guided-regimens-from-the-propel-phase-3-study/. Accessed October 1, 2023.

« Back to ISTH 2021 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/looking-beyond-fixed-dose-rurioctocog-alfa-pegol-prophylaxis-post-hoc-analysis-of-pk-guided-regimens-from-the-propel-phase-3-study/

Simple Search

Supported By:

Takeda logo

ISTH 2022 Congress site

Visit the official web site for the ISTH 2022 Virtual Congress »

  • Help & Support
  • About Us
  • Cookies & Privacy
  • Wiley Job Network
  • Terms & Conditions
  • Advertisers & Agents
Copyright © 2023 John Wiley & Sons, Inc. All Rights Reserved.
Wiley