OC 52.5 - Phase 3 HOPE-B trial of etranacogene dezaparvovec in severe/moderately severe hemophilia B: A post hoc responder analysis of participants who received full dose and responded to treatment

Tuesday, June 27, 2023

11:45 – 12:00 ET

Room: 710B

Session Available As: On-Demand

Presenting Author(s)

Steven W. Pipe, MD

Professor of Pediatrics and Pathology
University of Michigan, Ann Arbor, MI, USA
Ann Arbor, Michigan, United States

Co-Author(s)

Frank W.G. Leebeek, MD, PhD

Professor and Head of Department of Hematology
Erasmus MC, University Medical Center Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Michael Recht, MD, PhD, MBA (he/him/his)

Chief Medical and Scientific Officer
National Hemophilia Foundation
New York, New York, United States
NK

Nigel S. Key

Harold R. Roberts Distinguished Professor
Division of Hematology, University of North Carolina, Chapel Hill, NC, USA
Chapel Hill, North Carolina, United States
SL

Susan Lattimore

Regional Director of the Mountain States Hemophilia Network
Hemophilia Center, Oregon Health & Science University, Portland, OR, USA
Portland, Oregon, United States
Giancarlo Castaman, MD

Medical Director
Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy
Florence, Toscana, Italy
Michiel Coppens, MD, PhD (he/him/his)

Medical Specialist
Amsterdam University Medical Centers, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
YL

Yanyan Li

Director, Global Therapeutic Area Lead Statistician
CSL Behring, King of Prussia, PA, USA
King of Prussia, Pennsylvania, United States
PM

Paul E. Monahan

Senior Director, Clinical Development, Research and Development, Hematology
CSL Behring, King of Prussia, PA, USA
King of Prussia, Pennsylvania, United States
Wolfgang Miesbach, MD

Professor and Head of Coagulation Disorders and Comprehensive Care Centre
University Hospital Frankfurt, Frankfurt, Germany
Frankfurt, Hessen, Germany

Background: Based on the Phase 3 HOPE-B trial (NCT03569891), etranacogene dezaparvovec is the first gene therapy to obtain FDA approval for hemophilia B.

Aims: Post hoc analysis of participants responding to treatment in the HOPE-B trial.

Methods: In this open-label, single-arm study, adult males with hemophilia B (factor IX [FIX] ≤2%), with/without pre-existing adeno-associated virus 5 (AAV5) neutralizing antibodies (NAbs), received etranacogene dezaparvovec (single dose; 2x1013 gc/kg) after a ≥6-month lead-in period on FIX prophylaxis.

Results: Of 54 participants dosed (full analysis set [FAS]), two participants (one with AAV5 NAb titer 3,212 and one who received a partial dose [~10%]) did not respond to treatment. The remaining 52 (96.3%) participants received a full dose and responded to treatment (responders); these participants remained free from continuous FIX prophylaxis over 24 months. The results of this post hoc responder analysis align with those previously reported for the FAS.

Mean (standard deviation [SD]; min–max) FIX activity was 39.0 IU/dL (±18.7; 8.2–97.1) at Month 6 (n=51) and 36.7 IU/dL (±19.0; 4.7–99.2) at Month 24 (n=50). Mean annualized bleeding rate (ABR; all bleeds) for responders was 0.95 during Months 7–24, a 76% reduction from lead-in (mean ABR: 4.00; p< 0.0001). This is aligned with the FAS (64% reduction; p=0.0002). Responders experienced reductions in all bleed types (Table) and zero bleeds increased from 13 (25%) during lead-in to 27 (51.9%) during Months 7–24.

Mean (SD; min–max) unadjusted annualized FIX consumption for responders reduced by 99% from lead-in to Months 7–24: 262,077 (±149,818.0; 83,541–755,892) vs 3,682 (±7,124.6; 0–27,061) IU/year/participant (p < 0.0001). Over 24 months, 38/54 participants in the FAS experienced 93 treatment-related adverse events (none serious).

Conclusion(s): Over 24 months, single-dose etranacogene dezaparvovec resulted in stable FIX-Padua expression and significant reductions in ABR in both the FAS and responders.

Learning Objectives:

Upon completion, the participant will understand the responder population bleeding profile up to Month 24 in the Phase 3 HOPE-B study
Upon completion, the participant will understand the responder population FIX activity profile up to Month 24 in the Phase 3 HOPE-B study
Upon completion, the participant will understand the key safety data up to Month 24 in the Phase 3 HOPE-B study