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Randomized Controlled Trial
. 2021 Nov;27(6):921-931.
doi: 10.1111/hae.14419. Epub 2021 Oct 11.

The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors

Miguel Escobar  1 , Giancarlo Castaman  2 , Santiago Bonanad Boix  3 , Michael Callaghan  4 , Philippe de Moerloose  5 , Jonathan Ducore  6 , Cédric Hermans  7 , Janna Journeycake  8 , Cindy Leissinger  9 , James Luck  10 , Johnny Mahlangu  11 , Wolfgang Miesbach  12 , Ismail Haroon Mitha  13 , Claude Négrier  14 , Doris Quon  10 , Michael Recht  15   16 , Jean François Schved  17 , Amy D Shapiro  18 , Robert Sidonio Jr  19 , Alok Srivastava  20 , Oleksandra Stasyshyn  21 , Kateryna V Vilchevska  22 , Michael Wang  23 , Guy Young  24   25 , W Allan Alexander  26 , Ahmad Al-Sabbagh  27 , Daniel Bonzo  27 , Christopher Macie  28 , Thomas A Wilkinson  29 , Craig Kessler  30
Affiliations
Randomized Controlled Trial

The safety of activated eptacog beta in the management of bleeding episodes and perioperative haemostasis in adult and paediatric haemophilia patients with inhibitors

Miguel Escobar et al. Haemophilia. 2021 Nov.

Abstract

Introduction: Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (≥12 years of age). We describe here the EB safety profile from the three prospective Phase 3 clinical trials performed to date.

Aim: To assess EB safety, immunogenicity and thrombotic potential in children and adults who received EB for treatment of bleeding and perioperative care.

Methods: Using a randomized crossover design, 27 subjects in PERSEPT 1 (12-54 years) and 25 subjects in PERSEPT 2 (1-11 years) treated bleeding episodes with 75 or 225 μg/kg EB initially followed by 75 μg/kg dosing at predefined intervals as determined by clinical response. Twelve PERSEPT 3 subjects (2-56 years) received an initial preoperative infusion of 75 μg/kg (minor procedures) or 200 μg/kg EB (major surgeries) with subsequent 75 μg/kg doses administered intraoperatively and post-operatively as indicated. Descriptive statistics were used for data analyses.

Results: Sixty subjects who received 3388 EB doses in three trials were evaluated. EB was well tolerated, with no allergic, hypersensitivity, anaphylactic or thrombotic events reported and no neutralizing anti-EB antibodies detected. A death occurred during PERSEPT 3 and was determined to be unlikely related to EB treatment by the data monitoring committee.

Conclusion: Results from all three Phase 3 trials establish an excellent safety profile of EB in haemophilia A or B patients with inhibitors for treatment of bleeding and perioperative use.

Keywords: PERSEPT; SEVENFACT; eptacog beta; haemophilia; inhibitors; recombinant FVIIa; safety.

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Conflict of interest statement

M.E. has received honoraria for consulting and participating in advisory boards from BioMarin, Novo Nordisk, Genentech, Sanofi, Takeda, Pfizer, Kedrion, CSL Behring and NHF. G.C. has received honoraria as a speaker/participant on advisory boards for Alexion, Bayer, Shire/Takeda, CSL Behring, Novo Nordisk, Sobi, Roche, uniQure, Sanofi, Werfen, Kedrion, LFB and Grifols; M.C. has received grant/research support from Roche/Genentech; has participated in speaker's bureaus with Takeda, Genentech, Bayer and Novo Nordisk; has received honoraria from Takeda, Roche/Genentech, Pfizer, HEMA Biologics, Spark, BioMarin, Sanofi, Kedrion, Grifols and Bayer; is a major stock shareholder in Alnylum; and has served on advisory boards for Takeda, Roche/Genentech, Pfizer, HEMA Biologics, Spark, uniQure, BioMarin, Sanofi, Kedrion, Grifols and Bayer. P.d.M. has received consulting fees from Novo Nordisk, LFB and Bayer. J.D. has acted as a consultant for Bayer and HEMA Biologics, and has been on the speaker's bureau for Bayer. C.L. has received honoraria for advisory board participation for Bayer, Catalyst, CSL Behring, Genentech, Sanofi and Takeda. J.L. has acted as a paid consultant to Novo Nordisk. J.M. has received research grants from Bayer, Biogen, BioMarin, CSL, Novo Nordisk, Sobi, Roche and uniQure; has served on scientific advisory committees of Amgen, Bayer, Biotest, Biogen, Baxalta, CSL Behring, Catalyst Biosciences, Novo Nordisk, Roche and Spark; and has been a member of the speaker bureau of Alnylam, Bayer, Biotest, Biogen, Novo Nordisk, Pfizer, Sobi, Shire, Roche, ISTH and WFH. W.M. declares interests with Alnylam, Bayer, Biogen, Chugai, CSL Behring, Novo Nordisk, Octapharma, Pfizer, LFB, Roche, Takeda, Freeline, BioMarin, Sobi and uniQure. C.N. has received honoraria/consultation fees or grants/research support from Bayer, CSL Behring, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, Roche‐Chugai, Sanofi, Shire‐Takeda, Sobi and Spark Therapeutics. D.Q. had received honoraria/consulting fees from Bayer, BioMarin, Bioverativ/Sanofi, Catalyst, Novo Nordisk and Roche/Genentech; and has been on the speaker's bureau for BioMarin, Bioverativ/Sanofi, Novo Nordisk, Takeda, and Roche/Genentech. M.R.’s employers have received research funding from Bayer, BioMarin, CSL Behring, Genentech, Grifols, HEMA Biologics, LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi, Spark, Takeda and uniQure. M.R. has acted as a paid consultant to Catalyst Biosciences, CSL Behring, Genentech, HEMA Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda and uniQure. M.R. is on the board of directors of Foundation for Women and Girls with Blood Disorders and Partners in Bleeding Disorders. M.R. is an employee of the American Thrombosis and Hemostasis Network and Oregon Health & Science University. J.F.S has received grants from Pfizer, Bayer, Novo Nordisk and LFB, and has fees for consulting to Sobi. A.D.S. has served on advisory boards or as consultant for Genentech, Roche, Novo Nordisk, BioMarin, Bioverativ, Sanofi, ProMetric Bio Sciences, Sangamo, Sigilon and Takeda; and has received research funding from these organizations plus Agios, OPKO Global Bio Therapeutics, Kedrion, Octapharma and Novartis. R.F.S. has acted as a paid consultant for Takeda, Sanofi, Sobi, Catalyst, BioMarin, Novo Nordisk, Genentech, Octapharma, Bayer, Pfizer, Grifols, Kedrion and HEMA Biologics; and has investigator‐initiated grants from Grifols (Mexico Inhibitor Study), Takeda (ATHN 9), Genentech and Octapharma (Emi PUPs and Nuwiq ITI) and Octapharma (MOTIVATE study). A.S. has served as the chair of the DMC for this study. M.W. has been a consultant and/or advisor to Bioverativ/Sanofi, Takeda, CSL Behring, Catalyst Biosciences, Novo Nordisk, Bayer, Octapharma, Genentech, HEMA Biologics, BioMarin and uniQure, and was a study investigator for HEMA Biologics for research carried out in this work. G.Y. has received honoraria for consulting for Genentech/Roche and a grant from Genentech. G.Y. also has received honoraria from BioMarin, Grifols, Pfizer, Sanofi, Spark, and Takeda; and has grants from Grifols and Takeda. W.A.A. works as a consultant for HEMA Biologics, LLC, and has received fees for speaking and consulting. A.A‐S. and D.B. are employees of LFB‐USA. C.M. is an employee of HEMA Biologics, LLC. T.A.W. is a medical writer for GLOVAL LLC. C.K. received research support from Bayer, Genentech, Novo Nordisk, Octapharma and Takeda; and has served on advisory boards for Bayer, CSL, Genentech, Novo Nordisk, Octapharma, Takeda, Pfizer and HEMA Biologics. S.B.B., C.H., J.J., I.H.M., O.S. and K.V.V. have no competing interests to declare.

Figures

FIGURE 1
FIGURE 1
(A) Subject dispositions for PERSEPT 1 (green) and PERSEPT 2 (yellow). (B) Treatment protocol for mild and moderate bleeding episodes in PERSEPT 1 and PERSEPT 2. Dosing schedules for 75 and 225 μg/kg initial dose regimens (IDRs) are indicated
FIGURE 2
FIGURE 2
(A) Subject disposition in PERSEPT 3. (B) Treatment protocol for surgical procedures in PERSEPT 3
FIGURE 3
FIGURE 3
TEAEs and treatment‐related TEAEs per exposure episode following EB infusion, stratified by IDR (PERSEPT 1 and PERSEPT 2) or pre‐incision dose used in each surgery type (PERSEPT 3). Overall TEAEs and treatment‐related TEAEs per exposure episode from the three clinical trials (grouped by IDR or pre‐incision dose) are also shown
FIGURE 4
FIGURE 4
TEAEs and treatment‐related TEAEs per exposure episode following EB administration for both bleeding episode treatment and perioperative settings. The panel showing results from the perioperative setting is further subdivided into minor and major surgery groups
See this image and copyright information in PMC

References

    1. Astermark J. Overview of inhibitors. Semin Hematol. 2006;43(2 Suppl 4):S3‐7. - PubMed
    1. Male C, Andersson NG, Rafowicz A, et al. Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study. Haematologica. 2021;106(1):123‐129. - PMC - PubMed
    1. Ljung R, Auerswald G, Benson G, et al. Inhibitors in haemophilia A and B: management of bleeds, inhibitor eradication and strategies for difficult‐to‐treat patients. Eur J Haematol. 2019;102(2):111‐122. - PMC - PubMed
    1. Négrier C, Gomperts ED, Oldenburg J. The history of FEIBA: a lifetime of success in the treatment of haemophilia complicated by an inhibitor. Haemophilia. 2006;12(s5):4‐13.
    1. Hedner U. Recombinant activated factor VII: 30 years of research and innovation. Blood Rev. 2015;29 Suppl 1:S4‐8. - PubMed

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