Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials

Abstract

Introduction: Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half-life developed for prophylaxis, treatment of bleeds and perioperative management in patients with haemophilia A.

Aim: Evaluate the efficacy and safety of turoctocog alfa pegol treatment for major and minor surgeries in the pathfinder 3 and 5 phase III trials.

Methods: Adults/adolescents aged ≥12 years with severe haemophilia A (FVIII <1%) received perioperative turoctocog alfa pegol treatment planned to achieve FVIII activity levels >80% during major surgery (pathfinder 3). The primary end point was haemostatic efficacy during surgery; secondary end points were blood loss, haemostatic effect postsurgery, consumption, transfusions, safety and health economics. Children (0-11 years) undergoing minor surgeries received 20-75 IU/kg turoctocog alfa pegol at Investigator's discretion (pathfinder 5).

Results: pathfinder 3 included 35 patients undergoing 49 major surgeries. Haemostasis was successful in 47/49 (95.9%) surgeries; two had moderate haemostatic responses. Median (mean) blood loss during major surgery was 75 (322.6) mL. Four bleeds were reported postsurgery; three were successfully treated with turoctocog alfa pegol (one was not evaluated). On the day of surgery, overall mean (median) dose was 75.5 (74.5) IU/kg and mean (median) number of doses was 1.7 (2.0). Five procedures required 11 transfusions on the day of surgery or days 1-6. No safety concerns or inhibitors were identified. Forty-five minor surgeries in 23 children were performed without complications.

Conclusion: Turoctocog alfa pegol was effective for perioperative haemostatic management of major and minor surgeries in patients across age groups with severe haemophilia A.

Keywords: extended half-life; factor VIII; haemophilia A; haemostasis; surgery; turoctocog alfa pegol.

Conflict of interest statement

AT has participated in advisory boards for the following: Novo Nordisk, Roche and Werfen; and Speaker Bureaux of the following: Bayer, Novo Nordisk, Roche, Stago and Werfen. AN has participated in advisory boards for Baxalta (Shire), Genentech, HEMA Biologics and Novo Nordisk; a data and safety monitoring board for Pfizer. SRL has received grant support/personal fees and has served as a paid consultant for Novo Nordisk. ES has participated in advisory boards for Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, Shire/Takeda, SOBI, Spark and Uniqure; and Speaker Bureaux of the following: Bayer, Bioverativ, CSL Behring, Grifols, Kedrion, Novo Nordisk, Octapharma, Pfizer, Roche, Shire/Takeda and SOBI. LN has received honoraria from Baxalta (Shire), Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma and Pfizer, and acted as a consultant for Baxalta (Shire), Bayer, CSL Behring and Pfizer. JS has received speaker fees for Bayer, LEO Pharma and Novo Nordisk. KM has received research support from Bayer, Pfizer and Sanquin; speaker fees from Aspen, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb and Sanquin; and consulting fees from Uniqure. PC has received grants/research support from Bayer, CSL Behring, Freeline, Novo Nordisk, Pfizer and SOBI; and acted as a consultant for Bayer, Baxalta (Shire), Baxter, Bioverativ, Chugai, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, Sanofi, Shire and SOBI. CS is an employee of Novo Nordisk A/S. AL is an employee of Novo Nordisk A/S and holds shares with Novo Nordisk A/S. KH has participated in advisory boards for Bayer, Novo Nordisk and Octapharma.

© 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Surgical procedures completed in the pathfinder 3 trial (n = 49 procedures in 35 adults/adolescents). Among the 49 major surgeries, three were emergencies and the remaining 46 were elective

FIGURE 2

Estimated blood loss during major surgery for individuals in the pathfinder 3 trial. Estimated blood loss was reported for the surgery in general and not distinctly during the time from ‘knife to skin’ until ‘last stitch’. One patient with multiple comorbidities and a moderate haemostatic response had markedly higher blood loss (4520 mL) than the other patients 5