OC 47.4 - A Post Hoc Analysis of Individuals With Severe Hemophilia A and Inhibitors From the PUPs A-LONG Study

Monday, July 11, 2022

3:30 PM – 3:45 PM

Location: ExCel Center, ICC Capital Suite Room 2-4

Presentation Format: In-Person

Presenting Author(s)

Manuel Carcao, MD, FRCPC

Director, Haemophilia Clinic and Haemostasis Program
Hospital for Sick Children, Toronto, Canada
Toronto, Ontario, Canada

Co-Author(s)

MS

Michele Schiavulli

N/A
A.O.R.N. Santobono-Pausilipon
Napes, Campania, Italy
RK

Roshni Kulkarni

Physician
Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan, USA
East Lansing, Michigan, United States
PR

Pablo Rendo

Global Program Head
Sanofi
Waltham, Massachusetts, United States
MF

Meredith Foster

N/A
Sanofi
Cambridge, Massachusetts, United States
ES

Elena Santagostino

VP, Medicine Development Lead Haemophilia
Sobi, Stockholm, Sweden
Stockholm, Stockholms Lan, Sweden
SC

Sandra Casiano

Senior Global Medical Director
Sanofi, Cambridge, MA, USA
Cambridge, Massachusetts, United States
Königs Christoph, Dr. Dr.

Physician
Goethe University Frankfurt, University Hospital, Department of Pediatrics and Adolescent Medicine, Clinical and Molecular Haemostasis, Frankfurt am Main, Germany
Frankfurt, Hessen, Germany

Background: PUPs A-LONG evaluated extended half-life recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously untreated patients (PUPs) with severe hemophilia A.

Aims: Provide a descriptive post hoc analysis of inhibitor subjects from PUPs A-LONG.

Methods: PUPs A-LONG was an open-label, multicenter, Phase 3 study (NCT02234323) evaluating safety and efficacy of rFVIIIFc in male PUPs < 6 years old with severe hemophilia A. The primary endpoint was occurrence of inhibitor development, defined as 2 inhibitor tests of ≥0.6 BU/mL (low titer: ≥0.6 and < 5 BU/mL; high titer: ≥5 BU/mL) ≥2 weeks apart. Post hoc analyses included patient treatment regimen patterns and timing of inhibitor development, descriptive statistics of first inhibitor development, Kaplan–Meier analyses of time to first inhibitor-positive test by treatment regimen and by titer, and consumption.

Results: Twenty-eight of 103 subjects (27%) who received rFVIIIFc developed an inhibitor during PUPs A-LONG (Table 1). Twenty-four of these subjects were on prophylaxis as their final treatment regimen, of which 18 (75%) switched from on demand (Figure 1). Of 14 subjects with high-titer inhibitors (HTI), half (n=7) had prior low-titer inhibitors (LTI). Inhibitor development followed central venous access device (CVAD) placement in 17% of subjects who underwent the procedure (n=7/42) and in 20% of subjects who had intense factor exposure (IFE) (n=9/44). Five of 9 subjects (56%) experienced IFE due to CVAD placement (Table 1). Matching inhibitor-positive and -negative subjects with IFE by exposure days indicated no significant difference between groups in cumulative dose (IU/kg) administered until inhibitor development, nor was there correlation between groups (unmatched) for total consumption over time.

Conclusion(s): PUPs A-LONG post hoc analyses show half of HTI subjects initially develop LTI. The frequency of inhibitor development was comparable following IFE or CVAD placement, although analyses are based on limited patient numbers. Identifying factors that predispose individuals to inhibitor development remains a priority.