First Data From the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults With Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing
Highlights From the 62nd ASH Annual Meeting and Exposition

First Data From the Phase 3 HOPE-B Gene Therapy Trial: Efficacy and Safety of Etranacogene Dezaparvovec (AAV5-Padua hFIX variant; AMT-061) in Adults With Severe or Moderate-Severe Hemophilia B Treated Irrespective of Pre-Existing Anti-Capsid Neutralizing Antibodies

Steven W. Pipe, MD1, Michael Recht, MD, PhD2, Nigel S. Key, MD3, Frank W.G. Leebeek, MD, PhD4, Giancarlo Castaman, MD5, Susan U. Lattimore, RN6, Paul Van Der Valk7,8,9, Kathelijne Peerlinck, MD, PhD10, Michiel Coppens, MD11, Niamh O'Connell, MD, PhD12, John Pasi, MB, ChB, PhD, FRCP, FRCPath, FRCPCH13, Peter Kampmann, MD14, Karina Meijer, MD, PhD15, Annette von Drygalski, MD, PharmD16, Guy Young, MD17, Cedric Hermans, MD, MRCP, PhD18, Jan Astermark, MD, PhD19,20, Robert Klamroth, MD, PhD21, Richard S. Lemons, MD22, Nathan Visweshwar, MD23, Shelley Crary, MD, MS24, Rashid Kazmi, MBBS25, Emily Symington26, Miguel A. Escobar, MD27, Esteban Gomez, MD28, Rebecca Kruse-Jarres, MD29, Adam Kotowski, MD30, Doris Quon, MD, PhD31, Michael Wang, MD32, Allison P. Wheeler, MD33, Eileen K Sawyer, PhD34, Stephanie Verweij, BSc35, Valerie Colletta, MSc36, Naghmana Bajma, MD37, Robert Gut, MD, PhD36 and Wolfgang A. Miesbach, MD, PhD38

1University of Michigan, Ann Arbor, MI

2Oregon Health & Science University, Portland, OR

3University of North Carolina, Chapel Hill, NC

4Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands

5Azienda Ospedaliera Universitaria Careggi, Florence, Italy

6Oregon Health & Science University, Portland

7Vrije Universiteit Medical Center, Amsterdam, NLD

8Universitair Medisch Centrum Utrecht, Utrecht, Netherlands

9Van Creveldkliniek, University Medical Center Utrecht, Utrecht, Netherlands

10Department of Vascular Medicine and Haemostasis and Haemophilia Centre, University Hospitals Leuven, Leuven, Belgium

11Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands

12The National Coagulation Centre, St James Hospital, Dublin, Ireland

13Royal London Haemophilia Centre, Barts and the London School of Medicine and Dentistry, London, United Kingdom

14Rigshospitalet, Copenhagen, Denmark

15University Medical Center Groningen, Groningen, Netherlands

16University of California San Diego, La Jolla, CA

17University of Southern California Keck School of Medicine, Children's Hospital Los Angeles, Los Angeles, CA

18Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, Brussels, Belgium

19Department of Translational Medicine-Clinical Coagulation, Lund University, Malmo, Sweden

20Skane University Hospital, Malmo, Sweden

21Vivantes Klinikum im Friedrichshain, Berlin, Germany

22University of Utah, Salt Lake City, UT

23University of South Florida, Tampa, FL

24University of Arkansas for Medical Sciences, Little Rock, AR

25University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

26Cambridge University–Addenbrooke's Hospital, Cambridge, United Kingdom

27University of Texas Health Science Center at Houston, Houston, TX

28Phoenix Children's Hospital, Phoenix, AZ

29Bloodworks Northwest, Seattle, WA

30Hemophilia Center of Western New York, New York

31Los Angeles Orthopedic Hospital, Orthopedic Hemophilia Treatment Center, Los Angeles, CA

32Anschutz Medical Campus, University of Colorado, School of Medicine, Hemophilia and Thrombosis Center, Aurora, CO

33Vanderbilt University Medical Center, Nashville, TN

34uniQure Inc, Lexington, MA

35uniQure, Lexington, MA

36uniQure Inc, Lexington, MA

37Uniqure Inc, Lexington, MA

38University Hospital Frankfurt, Frankfurt, Germany

Key Data Points

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The HOPE-B phase 3 clinical trial for AMT-061 (etranacogene dezaparvovec) was designed as an open-label, single arm study. A single dose of AAV5-Padua hFIX was infused in 54 participants at a dose of 2x1013 gc/kg. The primary endpoints were FIX activity at 26 and 52 weeks post-infusion, and ABR at 52 weeks compared to lead-in. Duration of follow up is scheduled for 5 years. Pre-existing neutralizing antibodies to AAV5 was not an exclusion criterion.

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This figure shows mean and median FIX activity of all the participants up to 26 weeks post-dosing (N = 54), and for participants with follow up beyond 26 weeks (up to 72 weeks). Expression was robust by 3 weeks post-dosing and measured a mean of 37.2% at week 26. A number of participants have observations well beyond the 6-month co-primary endpoint with no evidence of decline of FIX activity in the follow-up period.

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This table compares bleeds for all participants during the first 6 months post-infusion to the 6 month lead-in period. Total bleeds decreased by 83% and treated bleeds decreased by 91%. Patients with 0 bleeds increased from 30% in the lead-in period to 72% in the 6 month post-dosing period.

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