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2469 Eptacog Beta Efficacy in Treating Mild or Moderate Bleeds in Target Joints of Individuals with Hemophilia A or B and Inhibitors in PERSEPT 1Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 322. Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Bleeding and Clotting, hemophilia, Diseases
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Mark T Reding, MD1, Maria Elisa Mancuso, MD, PhD2*, Suchitra Acharya, MD, MBBS3, Sanjay Ahuja, MD4, Maria Teresa Álvarez-Román, MD5*, Lisa N Boggio, MD, MS6, Meera B. Chitlur, MD7, Abraham Salvador Majluf-Cruz, MD8*, Amy L Dunn, MD9*, Miguel Escobar, MD10*, Annie Harroche, MD11*, Maissaa Janbain, MD12, Craig M. Kessler, MD13, Philip Maes, MD14*, Catherine E. McGuinn, MD15, Danielle Nance, MD16, Ulrike Nowak-Göttl, MD, PhD17*, Robert F. Sidonio, Jr., MD, MSc18, Duc Q Tran Jr., MD, MSc19, Michael Wang, MD20, Jerzy Windyga, MD, PhD21*, Hongying Wang, MS22*, Thomas Wilkinson, PhD23* and Steven W. Pipe, MD24

1Center for Bleeding and Clotting Disorders, University of Minnesota Medical Center, Minneapolis, MN
2Center for Thrombosis and Haemorrhagic Diseases, IRCCS Humanitas Research Hospital, Milan, Italy
3Cohen Children's Medical Center, Northwell Hemostasis and Thrombosis Center, Northwell Health, New Hyde Park, NY
4Division of Pediatric Hematology & Oncology, Rainbow Babies and Children's Hospital, Cleveland, OH
5Department of Hematology and Hemotherapy, Hospital Universitario La Paz, Autónoma University, Madrid, Spain
6Rush Hemophilia & Thrombophilia Center, Rush University Medical Center, Chicago, IL
7Central Michigan University College of Medicine/ Children's Hospital of Michigan, Carmen and Ann Adams Department of Pediatrics, Division of Hematology/Oncology, Detroit, MI
8Unidad de Investigacion Medica en Trombosis, Hemostasia y Aterogenesis, Instituto Mexicano del Seguro Social, Mexico City, Mexico
9Nationwide Children's Hospital, Columbus, OH
10University of Texas Health Science Center, Houston, TX
11Hemophilia Care Centre, Hematology Unit, Hôpital Universitaire Necker enfants malades, Paris, France
12Tulane University Health Sciences Center, New Orleans, LA
13Georgetown University Medical Centre, Washington, DC
14Paediatric Haematology and Oncology Department, University Hospital of Antwerp, Antwerp, Belgium
15Department of Pediatrics, Division of Pediatric Hematology Oncology, Weill Cornell Medicine, New York, NY
16Banner MD Anderson Cancer Center, Gilbert, AZ
17Institute of Clinical Chemistry, Thrombosis and Haemostasis Treatment Centre, University Hospital, Kiel-Lübeck, Germany
18Aflac Cancer and Blood Disorders, Department of Pediatrics, Emory University School of Medicine, Decatur, GA
19Department of Hematology and Medical Oncology, Hemophilia of Georgia Center for Bleeding & Clotting Disorders of Emory, Emory University School of Medicine, ATLANTA, GA
20Hemophilia and Thrombosis Center, University of Colorado Anschutz Medical Campus, Aurora, CO
21Department of Hemostasis Disorders and Internal Medicine, Laboratory of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw, Poland
22LFB-USA, Inc., Framingham, MA
23GLOVAL LLC, Monterey Park, CA
24University of Michigan, Ann Arbor, MI

Introduction

Recurrent bleeding in the same joint of a patient with hemophilia can lead to painful and chronic inflammation of the synovium, joint swelling, reduced range of motion, and in the long term joint arthropathy and irreversible joint damage. Early bleed resolution in the susceptible joint (known as a target joint) is thought to be crucial for preventing joint arthropathy and other incapacitating sequelae, and thus ultimately preserving joint function and health in persons with hemophilia.

Eptacog beta was FDA-approved in 2020 as a recombinant activated human factor VII for the treatment and control of bleeding episodes (BEs) in persons with hemophilia A or B and inhibitors (PwHABI) ages 12 years and older using two initial dose regimens (IDRs) of 75 or 225 µg/kg eptacog beta that were shown to be safe and efficacious. The pivotal phase 3 trial (PERSEPT 1; NCT02020369) included 27 PwHABI ages 12 to 54 years who treated 465 mild or moderate BEs, with treatment success proportions at 12 hours post-initial infusion of 82% and 91% for 75 and 225 µg/kg IDRs, respectively.

Objective

To evaluate eptacog beta efficacy when treating target and non-target joint BEs in PwHABI from PERSEPT 1, at 12 and 24 hours post-initial dose of eptacog beta.

Methods

PERSEPT 1 was a global, multicenter, open-label, prospective phase 3 trial using a crossover design (Wang et al., Haemophilia 23, pp. 832-43 [2017]). PwHABI who were not using prophylaxis were randomized to either the 75 or the 225 µg/kg IDR to treat BEs, and were crossed over to the alternate IDR every 3 months. Subjects in the 75 µg/kg IDR treated BEs with initial doses of 75 µg/kg eptacog beta followed by 75 µg/kg q3h as needed. Subjects in the 225 µg/kg IDR treated BEs with an initial 225 µg/kg eptacog beta dose, followed after 9 hours by 75 µg/kg q3h as needed. Mild or moderate BE treatment success at a given timepoint was defined as obtaining a hemostasis evaluation of “excellent” or “good” on a 4-point scale (“excellent” or “good” indicating hemostatic efficacy; “moderate” or “none" indicating lack of efficacy) with no additional eptacog beta being infused, no alternative hemostatic agents or blood products being used, and no increase in pain following the first “excellent” or “good” assessment. A target joint was defined in this trial as a joint in which recurrent bleeding had occurred on 4 or more occasions during the previous 6 months, or a joint in which 20 lifetime BEs had occurred.

Results

Twenty-seven PwHABI treated 396 mild or moderate joint BEs in PERSEPT 1; 17 of these subjects had been previously diagnosed with target joints. Of the 396 mild or moderate joint BEs treated, 135 were target joint bleeds (in 15 subjects) and 261 were non-target joint bleeds (in 25 subjects). At 12 hours post-initial infusion, target joint treatment success proportions and 95% confidence intervals (CIs) were 82% (95% CI: [63%, 100%]) and 93% (95% CI: 82%, 100%]) in the 75 and 225 µg/kg IDRs, respectively (Figure 1). Corresponding success proportions and CIs for non-target joint bleeds were 86% (95% CI: [75%, 97%]) and 95% (95% CI: [90%, 100%]), respectively. The increase in treatment success proportion observed at 12 hours with the 225 µg/kg IDR over the 75 µg/kg IDR was statistically significant for both target joint and non-target joint groups (p < 0.05). For both IDRs, the difference in treatment success proportions between target and non-target joint BEs was not statistically significant. Nearly all target (97-100%) and non-target joint bleeds (96-100%) were successfully treated at 24 hours post-initial eptacog beta infusion in each IDR (Figure 1).

Conclusions

The increase in both target and non-target joint bleed treatment success seen at 12 hours for the 225 µg/kg IDR over the 75 µg/kg IDR was statistically significant, and is consistent with a dose-dependent thrombin burst driving effective clot formation at the site of injury. While the 75 µg/kg IDR may be appropriate for certain patients, the 225 µg/kg IDR shows improved treatment success at 12 hours and may be the preferred choice in most circumstances. With the high efficacy seen at 24 hours, eptacog beta offers an important treatment option for treating both target and non-target joint BEs in PwHABI.

Disclosures: Reding: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hema Biologics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria; CSL Behring: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Consultancy, Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: medical writing support, Research Funding, Speakers Bureau. Ahuja: Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Membership on an entity's Board of Directors or advisory committees; ClotChip: Patents & Royalties; TraumaChek: Patents & Royalties; State of Ohio Rare Disease Advisory Council: Membership on an entity's Board of Directors or advisory committees. Chitlur: NovoNordisk: Consultancy, Honoraria; Agios Pharmaceuticals: Honoraria, Research Funding; BPL Inc: Honoraria; Emerging Therapeutics Inc: Honoraria; Genentech Pharmaceuticals: Honoraria, Research Funding; Sanofi/Genzyme Corp: Honoraria. Dunn: Genentech: Consultancy; Kedrion: Consultancy; CSL Behring: Consultancy; Biomarin: Consultancy, Research Funding; Takeda: Research Funding; Freeline: Research Funding; Novo Nordisk: Research Funding; Sanofi: Research Funding; American Society of Thrombosis and Hemostasis: Research Funding; World Federation of Hemophilia, USA: Membership on an entity's Board of Directors or advisory committees. Escobar: Genentech: Honoraria; CSL Behring: Honoraria; Bayer: Honoraria; Takeda: Honoraria; Novo Nordisk: Honoraria; UniQure: Honoraria; Sanofi: Honoraria; Kedrion: Honoraria; Hemobiologics/LFB: Honoraria; The National Hemophilia Foundation: Honoraria; Pfizer: Honoraria; BioMarin: Honoraria. McGuinn: Sanofi: Research Funding; Spark Therapeutics: Research Funding; Pfizer: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; HemaBiologics: Membership on an entity's Board of Directors or advisory committees; Genentech/ Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Berhing: Membership on an entity's Board of Directors or advisory committees; BPL: Consultancy; Takeda: Research Funding. Sidonio, Jr.: Novo Nordisk: Consultancy; Genentech: Consultancy, Research Funding; Biomarin: Consultancy; Catalyst: Consultancy; Sobi: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Octapharma: Consultancy, Research Funding; Bayer: Consultancy; Pfizer: Consultancy; Grifols: Consultancy, Research Funding; Kedrion: Consultancy; HEMA Biologics: Consultancy. Tran: Takeda: Consultancy; HEMA Biologics: Consultancy; Biomarin: Consultancy. Wang: Takeda: Consultancy, Other: principal investigator; Genentech: Consultancy, Other: principal investigator; Novo Nordisk: Consultancy, Other: principal investigator; CSL Behring: Consultancy, Other: principal investigator; Bioverativ: Consultancy, Other: principal investigator; Bayer: Consultancy, Other: principal investigator; BioMarin Pharmaceutical Inc.: Consultancy, Other: principal investigator; Pfizer/Spark: Consultancy, Other: principal investigator; Octapharma: Consultancy, Other: principal investigator; uniQure: Consultancy, Other: principal investigator; HEMA Biologics: Consultancy, Other: Clinical trial investigator. Windyga: Alnylam: Research Funding; Baxalta: Honoraria, Research Funding; Novo Nordisk: Honoraria, Research Funding; Octapharma: Honoraria, Research Funding; Rigel Pharmaceuticals: Research Funding; Roche: Honoraria, Research Funding; Shire/Takeda: Honoraria, Research Funding; Sobi: Honoraria, Research Funding; Alexion: Honoraria; CSL Behring: Honoraria; Ferring Pharmaceuticals: Honoraria; LFB: Honoraria; Sanofi/Genzyme: Honoraria; Siemens: Honoraria; Werfen: Honoraria. Wang: LFB-USA, Inc.: Current Employment. Wilkinson: GLOVAL, LLC: Consultancy. Pipe: Sanofi: Consultancy; Sangamo Therapeutics: Consultancy; UniQure: Consultancy; Regeneron/Intellia: Consultancy; Spark Therapeutics: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Apcintex: Consultancy; ASC Therapeutics: Consultancy; Roche/Genentech: Consultancy; Takeda: Consultancy; Pfizer: Consultancy; Freeline: Consultancy; HEMA Biologics: Consultancy; CSL Behring: Consultancy; BioMarin Pharmaceutical Inc.: Consultancy; Siemens: Research Funding; Yewsavin: Research Funding.

*signifies non-member of ASH