Follow-up of More Than 5 Years in a Cohort of Patients with Hemophilia B Treated with Fidanacogene Elaparvovec Adeno-Associated Virus Gene Therapy

Abstract Fifteen patients with moderately severe to severe hemophilia B (factor IX [FIX] activity ≤2%) were treated with fidanacogene elaparvovec at a dose of 5e11 vg/kg as part of a phase 1/2a study. The study was 52 weeks in duration, after which patients were eligible to enroll in the long-term follow-up (LTFU) study of up to 5 years. All 15 patients completed the phase 1/2a study, and 14 patients were subsequently enrolled in the LTFU study. At the time of the data cut (December 2020), 13 patients were enrolled in the LTFU study, with follow-up ranging from >2.5 years to >5 years following vector administration. Over this period of time, fidanacogene elaparvovec remained generally well tolerated. As reported previously, 3 patients were treated with corticosteroids within the first 6 months of the phase 1/2a study. No patients have required treatment or re-treatment with corticosteroids in the LTFU study. There were no serious adverse events (SAEs) in the phase 1/2a study, and 3 patients reported SAEs in the LTFU study, none of which were considered treatment related. No patient developed an inhibitor or had a thrombotic event. No patients have developed hepatic masses or significant elevations in alpha-fetoprotein (AFP). Annual liver ultrasounds revealed only hepatic steatosis in one patient. Mean FIX activity levels by year remain in the mild hemophilia severity range: 22.8%, year 1 (n=15); 25.4%, year 2 (n=14); 22.9%, year 3 (n=14); 24.9%, year 4 (n=9); and 19.8%, year 5 (n=7) when evaluated centrally using the ACTIN/FSL one-stage assay. These levels have been associated with mean annualized bleeding rates ranging from 0-0.9 over the course of follow-up, and no patients have resumed FIX prophylaxis. Four patients have undergone 6 surgical procedures during the LTFU study, 4 elective and 2 emergent. There were no bleeding complications with these procedures, and the 2 emergent procedures (appendectomy and lumbar discectomy) were performed without the need of additional FIX. Overall, this represents the largest cohort of hemophilia B patients with a duration of follow-up up to 5 years following treatment with an adeno-associated virus gene therapy expressing a highly active variant of FIX. Fidanacogene elaparvovec remains generally well tolerated over a period up to 5 years postinfusion. While encouraging, more long-term data in a larger cohort of patients are needed to further characterize the safety and durability of fidanacogene elaparvovec, which is under way in an ongoing phase 3 study. Disclosures Samelson-Jones: Pfizer: Consultancy, Research Funding; Spark: Research Funding. Sullivan: Genentech: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc.: Membership on an entity's Board of Directors or advisory committees; Biomarin: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees. Rasko: Imago: Consultancy; Cynata: Honoraria, Speakers Bureau; Gene Technology Technical Advisory Board: Membership on an entity's Board of Directors or advisory committees; NHMRC Mitochondrial Donation Expert Working Committee: Membership on an entity's Board of Directors or advisory committees; Australian Cancer Research: Membership on an entity's Board of Directors or advisory committees; Cure the Future Foundation: Membership on an entity's Board of Directors or advisory committees; FSHD Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Australian Government: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Pfizer Inc: Honoraria, Speakers Bureau; Glaxo-Smith-Kline: Honoraria, Speakers Bureau; Spark: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; bluebird bio: Honoraria, Speakers Bureau; Genea: Current equity holder in publicly-traded company; Celgene: Honoraria, Speakers Bureau. Giermasz: BioMarin: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy; Bayer: Consultancy; ATHN: Consultancy; NovoNordisk: Consultancy; UniQure: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Bioverativ/Sanofi: Consultancy, Research Funding, Speakers Bureau; Sangamo Therapeutics,: Research Funding. George: CSL Behring: Consultancy; Bayer: Consultancy; Avrobio: Other: Data Safety Monitoring Committee . Ducore: Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Speakers Bureau; HEMA Biologics: Consultancy, Honoraria. Teitel: Pfizer: Consultancy, Research Funding; Spark: Research Funding; Bayer: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Novo Nordisk: Consultancy; Octapharma: Consultancy; CSL Behring: Consultancy. McGuinn: Biogen: Research Funding; Roche/Genentech: Research Funding; Shire/Baxalta: Consultancy, Research Funding; Spark: Research Funding. O'Brien: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Winburn: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Smith: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Chhabra: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Rupon: Pfizer Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company.

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