Evaluation of Liver Health after Fidanacogene Elaparvovec Gene Therapy: Data from Study Participants with up to 5 Years of Follow-up

L.A. George^1,2, S.K. Sullivan³, J.E. Rasko⁴, A. Giermasz⁵, B.J. Samelson-Jones¹, J.M. Ducore⁵, J.M. Teitel⁶, C. E. McGuinn⁷, D. Rybin⁸, J.E. Murphy⁹, I. Winburn¹⁰, A. Chhabra⁹, J. Rupon¹¹

¹The Children's Hospital of Philadelphia, Philadelphia, United States, ²Perelman School of Medicine at the University of Pennsylvania, Philadelphia, United States, ³Mississippi Center for Advanced Medicine, Madison, United States, ⁴Royal Prince Alfred Hospital, SLHD, Sydney, Australia, ⁵University of California Davis, Sacramento, United States, ⁶St. Michael's Hospital, University of Toronto, Toronto, Canada, ⁷Weill Cornell Medical College, New York, United States, ⁸Pfizer Inc., Cambridge, United States, ⁹Pfizer Inc., New York, United States, ¹⁰Pfizer Ltd, Surrey, United Kingdom, ¹¹Pfizer Inc., Collegeville, United States

Abstract Number: PB0532

Meeting: ISTH 2021 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: Adeno-associated virus (AAV)–based gene therapy for the treatment of hemophilia has generally targeted hepatocytes. As such, liver health is an important aspect of screening assessments for these studies. The hemophilia population has a high percentage of patients with prior hepatitis C (HCV) and/or B (HBV) virus infections, which places additional importance on better understanding the role of AAV gene therapy on long-term liver health.

Aims: Evaluate liver health following fidanacogene elaparvovec, a hemophilia B gene therapy that utilizes a hepatotropic AAV vector.

Methods: Fidanacogene elaparvovec was administered to 15 adult males with moderately severe/severe hemophilia B as part of a phase 1/2a study and a subsequent long-term follow-up study (LTFU). Informed consent was obtained from all participants and both studies were reviewed and approved by an ethics committee. Patients with a history of HCV and/or HBV were eligible for study entry if liver health parameters were met. After completing the phase 1/2a study, 14/15 patients were enrolled in the LTFU for an additional follow-up of 5 years. One participant withdrew from LTFU study 3 years post- infusion.

Results: Ten of 14 participants who continued into the LTFU study had a history of resolved HCV, and seven participants also had prior HBV. With follow up ranging from 32 to 60 months, abnormalities on annual liver ultrasound included fatty liver in one participant. There were no significant elevations in plasma alfa-fetoprotein. Most common findings have been mild sustained elevations of alanine aminotransferase of uncertain etiology. FIX activity levels have remained relatively stable in these patients.

Conclusions: With up to 5 years of follow up, fidanacogene elaparvovec continues to be generally well tolerated. Long-term impacts to overall liver health currently appear to be mild in patients with moderately severe/severe hemophilia B. Longer term monitoring is ongoing to consolidate this initial result.

To cite this abstract in AMA style:

George LA, Sullivan SK, Rasko JE, Giermasz A, Samelson-Jones BJ, Ducore JM, Teitel JM, McGuinn CE, Rybin D, Murphy JE, Winburn I, Chhabra A, Rupon J. Evaluation of Liver Health after Fidanacogene Elaparvovec Gene Therapy: Data from Study Participants with up to 5 Years of Follow-up [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/evaluation-of-liver-health-after-fidanacogene-elaparvovec-gene-therapy-data-from-study-participants-with-up-to-5-years-of-follow-up/. Accessed November 29, 2023.

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