Gene therapy with fidanacogene elaparvovec leads to less bleeding in hemophilia B – NTVH

Gene therapy with fidanacogen elaparvovec leads to less bleeding than FIX prophylaxis in adult patients with hemophilia B. This is the conclusion of Adam Cuker (Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA) and colleagues. research based on the results of the BENEGENE – 2 study, recently published in The New England Journal of Medicine.

ANIMAL-2

Fidanacogene elaparvovec is an adenoviral vector (AAV) designed to carry the highly active transgene FIX-R338Leither FIX-Paduato express and express. In the international phase III study BENEGENE-2, patients with hemophilia B received fidanacogen elaparvovec (5 x 10).¹¹ genome copies per kg of body weight) given intravenously. Participants were men aged 18-65 years with moderate or severe hemophilia (FIX activity ≤2%) who had received at least 6 months of FIX prophylaxis in the pre-entry BENEGENE-1 study. Patients with neutralizing anti-AAV antibodies or FIX inhibitors, among others, were excluded from participation. The primary outcome measure was the annual bleeding rate (ABR), measured from 12 weeks to 15 months after the infusion and compared to the pre-infusion rate. Primary secondary outcome measures were the ABR of treated bleeding, annual exogenous FIX infusion frequency (AIR) and FIX activity. The safety of gene therapy was also evaluated.

A total of 45 patients received fidanacogene elaparvovec (mean age: 33.2 years), of which 44 patients were followed for at least 15 months. Gene therapy with fidanacogen elaparvovec resulted in a 71% lower ABR in the post-infusion phase compared to FIX prophylaxis in the pre-infusion phase (1.28 vs. 4.42; difference). [95%-BI]):-3,15 [-5,46 tot -0,83; p=0,008). De ABR van behandelde bloedingen daalde met 78%, van 3,34 in de pre-infusiefase naar 0,73 in de post-infusiefase (verschil [95%-BI]): -2,61 [-4,27 tot -0,96]; p=0.002). Also, treatment with fidanacogene elaparvovec resulted in a 92% lower AIR of exogenous FIX in the post-infusion phase, compared to FIX prophylaxis in the pre-infusion phase (4.54 vs. 58.83; difference). [95%-BI]:-54,29 [-63,58 tot -45,01]; p

Bad events

One or more adverse events (AEs) occurred in 38 patients (84%), the most common being elevated ALT concentration (27%). 28 patients (62%) had to be treated with glucocorticoids due to increased ALT concentration and/or decreased FIX activity. One or more serious AEs occurred in 7 patients (16%). None of the AE patients developed a serious infusion, thrombotic event, FIX inhibitors or malignancy.

Reference

Cuker A, Kavakli K, Frenzel L, et al; BENEGENE-2 Test investigators. Gene therapy with fidanacogene elaparvovec in adults with hemophilia B. N Engl J Med 2024; 391: 1108-18.