Recent Progress in the Development of AMT-061 (Etranacogene Dezaparvovec) for Persons With Severe or Moderately Severe Hemophilia B

Recent Progress in the Development of AMT-061 (Etranacogene Dezaparvovec) for Persons With Severe or Moderately Severe Hemophilia B
Highlights from the WFH Virtual Summit 2020

Recent Progress in the Development of AMT-061 (Etranacogene Dezaparvovec) for Persons With Severe or Moderately Severe Hemophilia B

Steven W. Pipe,1 Wolfgang Miesbach,2 Annette Von Drygalski,3 Adam Giermasz,4 Karina Meijer,5 Michiel Coppens,6 Peter Kampmann,7 Robert Klamroth,8 Roger Schutgens,9 Nigel S. Key,10 Susan Lattimore,11 Michael Recht,12 Esteban Gomez,13 Giancarlo Castaman,14 Eileen K. Sawyer,12 Robert Gut,12 Frank W.G. Leebeek15

1University of Michigan, Ann Arbor, USA

2University Hospital Frankfurt, Frankfurt, Germany

3University of California San Diego, San Diego, USA

4University of California Davis, Sacramento, USA

5University Medical Center Groningen, Groningen, the Netherlands

6Academic Medical Center, Amsterdam, The Netherlands

7Rigshospitalet, Copenhagen, Denmark

8Vivantes Klinikum, Berlin, Germany

9University Medical Center, Utrecht, Netherlands

10University of North Carolina, Chapel Hill, USA

11Oregon Health & Science University, Portland, USA

12uniQure biopharma B.V., Lexington, MA, USA

13Phoenix Children’s Hospital, Phoenix USA

14Azienda Ospedaliera Universitaria Careggi, Florence, Italy

15Erasmus University Medical Center, Rotterdam, The Netherlands

Key Data Points

This diagram summarizes the design for studies testing both AMT-060 and AMT-061 (etranacogene dezaparvovec). Both studies included men with hemophilia B and FIX levels ≤ 2%. Clinical severity was based on FIX prophylaxis or ≥ 4 bleeds/year or hemophilic arthropathy. Although the presence of AAV5 NAbs was an exclusion criterion for AMT-060 trials, 3 participants in the low dose cohort were found to have had detectable titers before initiation of dosing, with no impact on safety or efficacy. As a result, the presence of AAV5 NAbs was not an exclusion criterion for AMT-061 trials. AMT-060 was tested at 2 doses and AMT-061 was tested at the higher of the 2 doses.

Patients in the low dose and high dose cohorts showed dose-dependent, sustained increases in expression of FIX for up to 4 years, with a mean of 5% for the low dose group and 7.5% for the high dose group. Patients also demonstrated a sustained reduction in FIX usage. Of the 9 participants using FIX prophylaxis at study entry, 8 were FIX prophylaxis-free at last follow up.

Patients treated with a single infusion of AMT-061 have demonstrated sustained increases in FIX activity levels for up 52 weeks. The mean FIX activity level for the 3 participants after 1 year of follow up was in the functionally curative range of 41%. All 3 participants have also experienced reductions in FIX usage and have discontinued routine use of prophylaxis.

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