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509 Final Results of PUPs A-LONG Study: Evaluating Safety and Efficacy of rFVIIIFc in Previously Untreated Patients with Haemophilia A

Program: Oral and Poster Abstracts
Type: Oral
Session: 322. Disorders of Coagulation or Fibrinolysis: Hemophilia: Treatment and Inhibitors
Hematology Disease Topics & Pathways:
Anemias, Bleeding Disorders, Hemophilia, Biological, Diseases, Bleeding and Clotting, Therapies, Clinically relevant
Monday, December 7, 2020: 7:30 AM

Christoph Koenigs1*, Margareth C. Ozelo2, Amy Dunn3, Roshni Kulkarni, MD4, Beatrice Nolan, FRCPath5*, Simon A. Brown6*, Raina Liesner7*, Michele Schiavulli8*, Sriya Gunawardena9*, Sutirtha Mukhopadhyay10*, Deepthi Jayawardene9*, Bent Winding11* and Manuel Carcao12

1Department of Pediatrics and Adolescent Medicine, University Hospital Frankfurt, Frankfurt, Germany
2University of Campinas, São Paulo, Brazil
3Nationwide Children's Hospital, Columbus, OH
4Michigan State University, East Lansing, MI
5Children Health Ireland at Crumlin, Dublin, Ireland
6Queensland Children’s Hospital, South Brisbane, QLD, Australia
7Great Ormond Street Hospital, London, United Kingdom
8A.O.R.N. Santobono-Pausilipon, Naples, Italy
9Sanofi, Waltham, MA
10Sanofi, Gent, Belgium
11Swedish Orphan Biovitrum AB (Sobi), Stockholm, Sweden
12Hospital for Sick Children, Toronto, Canada


PUPs A-LONG is the first study evaluating an extended half-life (EHL), recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously untreated patients (PUPs) with hemophilia A. The safety, including inhibitor development, and efficacy of rFVIIIFc in PUPs was evaluated.


This open-label, multicenter, Phase 3 study (NCT02234323) enrolled male PUPs <6 years of age with hemophilia A (<1 IU/dL endogenous FVIII) to receive rFVIIIFc. The primary endpoint was inhibitor development (incidence rate=number of patients with inhibitor/number of patients reaching ≥10 exposure days [ED] milestone or with inhibitor). A secondary endpoint was annualized bleed rate (ABR).


Of 103 patients receiving ≥1 dose, 80 (77.7%) were <1 year of age; 20 (19.4%) had a family history of inhibitors; and 82 (79.6%) had a high-risk hemophilia genotype. Eighty-one patients started with on-demand treatment; of these, 69 switched to prophylaxis. Twenty patients started on prophylaxis and 2 were not assigned a regimen. Eighty-seven (84.5%) patients completed the study. Eighty-seven (84.5%), 85 (82.5%), and 81 (78.6%) patients had ≥10, ≥20, ≥50 EDs to rFVIIIFc, respectively. Total and high-titer (≥5.00 BU/mL) inhibitor rates were 31.1% (28/90) and 15.6% (14/90), respectively, for patients with ≥10 EDs (3 inhibitor patients with <10 EDs were included). Median time to inhibitor development was 9 EDs (range: 1–53). rFVIIIFc dosing and efficacy data are shown in Table 1. Twenty-eight (27.2%) patients had 32 adverse events assessed as related by the investigator: FVIII inhibition (n=28); soft tissue hemorrhage (n=1); deep vein thrombosis (n=1); device-related thrombosis (n=1); rash papular (n=1). There was 1 non–treatment-related death due to intracranial hemorrhage (onset during screening period prior to first rFVIIIFc dose).


This was the first prospective study of an EHL rFVIIIFc treatment for PUPs with severe hemophilia A. Overall inhibitor development was in the range that can be expected, although the high-titer incidence was lower than that reported in the literature. The data demonstrate that rFVIIIFc was well tolerated and effective in this pediatric patient population.

Disclosures: Koenigs: Bayer Vital GmbH, Biotest, CSL Behring, Intersero, Novo Nordisk, Pfizer, Sanofi/Sobi, and Takeda: Other: grants; Bayer Vital GmbH, CSL Behring, Novo Nordisk, Roche/Chugai, Sanofi/Sobi and Takeda: Other: personal fees. Ozelo: Roche: Consultancy, Research Funding, Speakers Bureau; Shire/Takeda: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding; BioMarin: Consultancy, Research Funding, Speakers Bureau; Bioverativ/Sanofi: Consultancy, Research Funding; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau. Dunn: World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Spire: Honoraria; ATHN: Research Funding; Takeda: Research Funding; BioMarin: Research Funding; uniQure: Consultancy; Genentech, Inc.: Consultancy; Nationwide Children's Hospital: Current Employment. Kulkarni: Sanofi/ Bioverativ, Bayer, Biomarin, Shire/Takeda, Novo Nordisk, Freeline: Other: clinical trial research grants ; Bioverativ/Sanofi, BPL, Genentech, Kedrion, Novo Nordisk, Octapharma, Pfizer, Takeda, Catalyst Bioscience Bayer: Membership on an entity's Board of Directors or advisory committees. Nolan: Sanofi: Other: PI for sponsor-(Sanofi-) led clinical trial; Bayer, CSL Behring, and Sanofi.: Other: sponsorship; Sobi: Other: personal fees. Liesner: Sobi, Octapharma, CSL Behring, Grifols, Shire/Takeda, Novo Nordisk, Bayer, and Roche.: Other: personal fees. Schiavulli: Bayer, CSL Behring, Kedrion, Roche/Chugai and Sobi: Other: personal/speaker fees, Speakers Bureau; CSL Behring, Novo Nordisk, Roche/Chugai, and Sobi.: Membership on an entity's Board of Directors or advisory committees. Gunawardena: Sanofi: Current Employment. Mukhopadhyay: Sanofi: Current Employment. Jayawardene: Sanofi: Current Employment. Winding: Sobi AB: Current Employment. Carcao: Bayer, Bioverativ/Sanofi, CSL-Behring, Novo Nordisk, Octapharma, Pfizer, and Shire/Takeda: Research Funding; Bayer, Bioverativ/Sanofi, Biotest, CSL Behring, Grifols, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, and Shire/Takeda.: Honoraria, Speakers Bureau.

*signifies non-member of ASH