Presentation Details
| A Multi-Year Follow-up Study of Fidanacogene Elaparvovec Gene Therapy for Hemophilia B Benjamin J.Samelson-Jones1, 2, Lindsey A.George1, 2, John E.J.Rasko3, 4, Adam Giermasz5, Jerome M.Teitel6, Catherine E.McGuinn7, Jonathan M.Ducore5, Sharon Pennington8, Katherine A.High2, Jeremy Rupon9, Francesca Biondo10, Annie Fang11, Lynne M.Smith9, Matko Kalac11, Amit Chhabra11, Frank Plonski9. 1Children’s Hospital of Philadelphia, Philadelphia, PA, USA.2Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.3Department of Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney, Australia.4Gene and Stem Cell Therapy Program, Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.5Hemophilia Treatment Center, University of California Davis, Sacramento, CA, USA.6St.Michael’s Hospital, University of Toronto, Toronto, ON, Canada.7Weill Cornell Medicine, New York, NY, USA.8Mississippi Center for Advanced Medicine, Madison, MS, USA.9Pfizer Inc, Collegeville, PA, USA.10Pfizer Srl, Rome, Italy.11Pfizer Inc, New York, NY, USA |
Abstract
Background: Fidanacogene elaparvovec is a recombinant adeno-associated virus gene therapy vector for hemophilia B that delivers a high-activity factor IX (FIX) variant (R338L). In a phase 1/2a study (NCT02484092), participants safely achieved therapeutic levels of FIX expression with low-dose vector administration. A long-term follow-up (LTFU) study (NCT03307980) was initiated to assess the multi-year safety and efficacy of fidanacogene elaparvovec in these participants. Objective: To report results from participants followed up to 6 years in the LTFU study. Methods: Fifteen participants with moderately severe to severe hemophilia B (FIX activity ≤2%) were treated with 5e11 vg/kg fidanacogene elaparvovec in a phase 1/2a study (1-year duration) and were then eligible to enroll in a LTFU for 5 additional years. Results: All 15 participants completed the phase 1/2a study, and 14 were enrolled in the LTFU. As of August 2023, all 14 participants completed ≥3 years of follow-up post infusion. Seven participants completed 6 years of follow-up, 2 discontinued from the study, 1 was lost to follow-up, and 4 remain ongoing in the trial. Nine serious adverse events (AEs) were reported in 4 participants; none were deemed treatment-related, and each occurred >1 year post infusion. No AE resulted in study discontinuation or death. After the first year post infusion, asymptomatic liver enzyme levels above the normal range were reported in 9 participants; none of these events were treated with corticosteroids. No liver masses or malignancies, thrombotic events, or FIX inhibitors were reported. Geometric mean FIX activity (measured with Actin-FSL one-stage assay) remained in the mild range post infusion (Table 1). Annualized bleeding rates (ABRs) were low throughout the duration of follow-up (Table 2). During the LTFU, 10 participants (71%) had no bleeding events. Four participants experienced a total of 24 bleeding events (17 spontaneous, 7 traumatic). Overall, bleeding events occurred when FIX activity levels were less than ~25%. Bleeds into joints tended to be in arthropathic and/or target joints. No participant resumed FIX prophylaxis. Conclusions: Fidanacogene elaparvovec demonstrated long-term efficacy and was well tolerated over 3–6 years, reflecting the longest follow-up of participants with hemophilia B in a gene therapy trial. A phase 3 study is ongoing to further investigate these findings.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.