Fidanacogene Elaparvovec Well-Tolerated in Hemophilia B


No concerning effects to liver health were observed in the phase 1/2a study.

Fidanacogene elaparvovec is well tolerated in patients with hemophilia B, with mild long-term effects on liver health, according to data from a recent study.1

These data, from a phase 1/2a study (NCT03861273) and a subsequent long-term follow-up (LTFU) study, were presented at the International Society on Thrombosis and Haemostasis (ISTH) 2021 Congress by Lindsey A. George, MD, attending physician, Division of Hematology, Children's Hospital of Philadelphia. The study aimed to evaluate liver health following treatment with fidanacogene elaparvovec, which utilizes a hepatotropic Adeno-associated virus (AAV) vector.

"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,” George and colleagues wrote.

The study enrolled 15 adult male patients with moderate to severe hemophilia B that were administered fidanacogene elaparvovec and 14 into the LTFU. One participant withdrew from the LTFU 3 years post-infusion. Of the participants in the LTFU, 10 had prior resolved HCV and 7 had prior HBV. Patients were followed for between 32 and 60 months.

READ MORE: Valoctocogene Roxaparvovec’s Treatment Durability in Hemophilia A in Question

Common safety findings included mild sustained elevations of alanine aminotransferase of uncertain etiology. Annual liver ultrasounds were conducted; these revealed fatty liver in 1 participant. No significant elevations in plasma alfa-fetoprotein were observed. Factor IX (FIX) activity has remained relatively stable in all participants.

“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,” George and colleagues concluded.

Findings from other gene therapies for hemophilia B were also presented at ISTH. These included efficacy findings of AMT-060, which was seen to produce stable FIX expression and sustained reductions in bleeding over 5 years of follow-up.2

Patients that received a 5 x 1012 gc/kg dose of AMT-060 had a mean FIX activity of 5.2% through 5 years compared with patients who received a 2 x 1013 gc/kg dose and had a mean FIX activity of 7.2% through 5 years. Additionally, during the last 12 and 6 months of observation, lower-dose participants had a mean annualized bleeding rate (ABR) of 6.5 and higher-dose patients had a mean ABR of 0.0, representing a 55% and 100% reduction in ABR compared with the year before treatment, respectively.

AMT-060 was also found to be well-tolerated. No participants developed FIX inhibitors or signs of sustained AAV5 capsid-specific T-cell activation. Treatment-related AEs mostly occurred in the first 3.5 months after treatment. These included 3 cases of transient mild alanine aminotransferase. Final 5-year data will be presented at a later date. Study participants will also be able to enroll in a LTFU study over an additional 5 years.

1. George LA, Sullivan SK, Rasko JE, et al. Evaluation of liver health after fidanacogene elaparvovec gene therapy: Data from study participants with up to 5 years of follow-up. Presented at ISTH 2021 Congress; July 17-21. Abstract PB0532.
2. Miesbach W, Meijer K, Coppens M, et al. Five year data confirms stable FIX expression and sustained reductions in bleeding and factor IX use following AMT-060 gene therapy in adults with severe or moderate-severe Hemophilia B. Presented at ISTH 2021 Congress; July 17-21. Abstract OC 26.3
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