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506 Once-Weekly Efanesoctocog Alfa Prophylaxis Provided High Sustained Factor VIII Activity Levels, Independent of Blood Group, in Children <12 Years of Age with Severe Hemophilia AClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 322. Disorders of Coagulation or Fibrinolysis: Clinical and Epidemiological: Bleeding Disorder Management Throughout the Lifespan
Hematology Disease Topics & Pathways:
Research, clinical trials, Bleeding and Clotting, hemophilia, Clinical Research, Diseases
Sunday, December 10, 2023: 12:15 PM

Flora Peyvandi, Prof1, Cristina Tarango2, Mindy Simpson3*, Manuela Albisetti4*, Maria Teresa Álvarez-Roman5*, Anthony KC Chan, MBBS6, Julie Curtin7*, Linda Bystrická8*, Elena Santagostino9, Ekaterina Gresko9*, Sriya Gunawardena10*, Chandravathi Vage11* and Nancy Wong11*

1Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
2Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH
3Rush University Medical Center, Rush Hemophilia and Thrombophilia Center, Chicago, IL
4Department of Hematology, University Children's Hospital, Zurich, Switzerland
5Hospital Universitario La Paz, Autonoma University of Madrid, IdiPAZ, Madrid, Spain
6McMaster Children's Hospital, McMaster University, Hamilton, ON, Canada
7The Children's Hospital at Westmead, Sydney, NSW, Australia
8Sobi, Stockholm, Sweden
9Sobi, Basel, Switzerland
10Sanofi, Bridgewater
11Sanofi, Bridgewater, NJ

Introduction

Efanesoctocog alfa is a new class of factor VIII (FVIII) replacement therapy uniquely designed to overcome the von Willebrand factor–imposed FVIII half-life ceiling. In the Phase 3 XTEND-Kids study in previously treated children <12 years of age with severe hemophilia A, efanesoctocog alfa was well tolerated and FVIII inhibitor development was not detected. Furthermore, once-weekly efanesoctocog alfa 50 IU/kg provided highly effective bleed protection and treatment. These results are consistent with the results of the Phase 3 XTEND-1 study in adolescents and adults with severe hemophilia A.

Objective

To characterize the pharmacokinetics (PK) of efanesoctocog alfa in children <12 years of age with severe hemophilia A in the XTEND-Kids study (NCT04759131).

Methods

The XTEND-Kids study enrolled children with severe hemophilia A (<1 IU/dL endogenous FVIII activity) previously treated with FVIII replacement products or cryoprecipitate for ≥150 exposure days (6–<12 years) or ≥50 exposure days (<6 years). Participants received once-weekly efanesoctocog alfa
50 IU/kg for 52 weeks. FVIII activity levels were assessed using the activated partial thromboplastin time–based one-stage clotting assay with the reagent Actin FSL. PK parameters after the first dose were estimated for the 37 participants in the PK subgroup using non-compartmental analysis. Mean peak and trough FVIII activity levels were determined for all participants by visit. Time to FVIII activity levels at steady state (Week 26) was determined using population modelling.

Results

A total of 74 participants were enrolled in XTEND-Kids; of these, 37 were included in the PK subgroup (n=19, <6 years; n=18, ≥6–<12 years). At the end of the first weekly dosing interval, mean (standard deviation [SD]) FVIII activity levels were 5.73 (1.63) IU/dL in participants <6 years and 6.93 (1.76) IU/dL in those ≥6–<12 years (Figure). After the first dose of efanesoctocog alfa, mean (SD) half-life was 38.0 (3.72) and 42.4 (3.70) hours, and mean (SD) clearance was 0.742 (0.121) and 0.681 (0.139) mL/h/kg in participants <6 years and ≥6–<12 years, respectively (Table). Incremental recovery values remained consistent throughout the study, ranging from 2.12 to 2.35 IU/dL per IU/kg. Mean (SD) areas under the activity-time curve over the dosing interval (AUC0-tau) were 6800 (1120) and 7190 (1450) h*IU/dL in participants <6 years and ≥6–<12 years, respectively. Mean (SD) clearance after first dose was similar between participants with blood group O and non-O, 0.76 (0.12) versus 0.68 (0.15) mL/h/kg (Table). Half-life was also similar; mean (SD) half-life was 40.2 (4.45) hours in participants with blood group O, and 40.0 (4.17) hours in those with a non-O group. In the overall study population, mean trough (pre-dose) FVIII activity levels ranged from 8.54 IU/dL at Week 4 to 13.7 IU/dL at Week 52. Across all visits mean FVIII activity levels 15 minutes post-dose were consistently below 150 IU/dL. Mean FVIII activity levels at steady state (Week 26) remained >40 IU/dL for 3 days and >10 IU/dL for ~7 days following a 50 IU/kg weekly dose of efanesoctocog alfa.

Conclusions

PK parameters and the mean FVIII activity-time profile were similar for participants <6 years and ≥6–<12 years of age. No clinically relevant differences in PK parameters were observed between participants with blood group O and non-O. At steady state (Week 26), FVIII activity levels were maintained in the normal to near-normal range (>40 IU/dL) for 3 days and remained >10 IU/dL for ~7 days following a 50 IU/kg dose of efanesoctocog alfa. Once-weekly prophylaxis with efanesoctocog alfa provided high sustained FVIII levels across the week for children <12 years of age in the XTEND-Kids study.

Disclosures: Peyvandi: Biomarin: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Spark: Speakers Bureau; Takeda: Speakers Bureau. Tarango: Sanofi: Honoraria; Bayer: Membership on an entity's Board of Directors or advisory committees. Simpson: CSL Behring: Consultancy; Genentech: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Octapharma: Research Funding; Pfizer: Consultancy; Sanofi: Consultancy. Albisetti: Sobi: Other: Travel support ISTH 2023. Álvarez-Roman: Novo Nordisk: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; LFB: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Grifols: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau. Chan: Bayer: Honoraria, Other: Clinical trial; Novo Nordisk: Honoraria, Other: Clnical trial, Research Funding; Takeda: Honoraria, Other: Clinical triial; Pfizer: Honoraria, Other: Clinical trial; ATTWILL: Patents & Royalties; Centessa Pharmaceuticals: Other: Clinical trial; Sanofi: Honoraria, Other: Clinical trial. Curtin: Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Bystrická: Swedish Orphan Biovitrum AB: Current Employment, Current equity holder in publicly-traded company. Santagostino: Swedish Orphan Biovitrum: Current Employment. Gresko: Swedish Orphan Biovitrum AB: Current Employment. Gunawardena: Sanofi: Current Employment, Current equity holder in publicly-traded company. Vage: Sanofi: Current Employment. Wong: Sanofi: Current Employment, Current equity holder in publicly-traded company.

*signifies non-member of ASH