The use of the factor VIII (FVIII) replacement therapy N8-GP in previously untreated patients (PUPs) was associated with inhibitor development that was considered by investigators to be in the expected range in a new study. Study results were reported in the journal Blood Advances.
N8-GP, or turoctocog alfa pegol, is a recombinant and glycoPEGylated FVIII replacement product that has an extended half-life for use in patients with hemophilia A. The study investigators noted in their report that PUPs who have severe hemophilia A are at a particular risk of developing inhibitors in the first 50 to 75 exposure days when receiving FVIII replacement therapy. They undertook this study to evaluate immunogenicity and other outcomes with N8-GP in PUPs with severe hemophilia A.
The single-arm, open-label, phase 3 pathfinder6 study (ClinicalTrials.gov Identifier: NCT02137850) enrolled PUPs below the age of 6 years with severe hemophilia A. The immunogenicity, safety, and efficacy of N8-GP are being evaluated in this study that has a primary endpoint of the incidence of FVIII inhibitors (at a level of ≥0.6 Bethesda units [BU]). The study is ongoing.
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At least 1 dose of N8-GP was received by 80 patients in this study, of whom 50 or more patients had reached at least 50 exposure days with N8-GP. The study population had a mean baseline age of 10.4 months. Among 67 patients who were evaluable for inhibitor incidence, the incidence of FVIII inhibitors was 29.9%, with 14.9% showing a high inhibitor titer (>5 BU).
N8-GP prophylaxis was given over a mean of 2.17 years in 65 patients. These patients had a median annualized bleeding rate of 1.42 (interquartile range [IQR], 0.76-3.13), with a hemostatic success rate of 90.5% across bleeding episodes during the prophylaxis period. The median annual bleeding rate had been 6.63 (IQR, 2.61-13.04) in the pre-prophylaxis period.
Adverse events (AEs) were reported in 93.8% of the patient population, with 70 serious AEs reported in 45 of the patients. FVIII inhibitor development was the most frequent serious AE. Post hoc analysis revealed a temporarily decreased incremental recovery rate in 17 patients during the first 5 exposure days to N8-GP. Decreased incremental recovery was also considered to have a strong temporal correlation with anti-polyethylene glycol immunoglobulin G antibody titers.
“In conclusion, the incidence of inhibitors in PUPs treated with N8-GP was within the expected range, and the incidence of high-titer inhibitors was within the lower expected range,” the study investigators wrote in their report. They also considered N8-GP use to show efficacy in PUPs in preventing and treating bleeding episodes.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Reference
Male C, Königs C, Dey S, et al. The safety and efficacy of N8-GP (turoctocog alfa pegol) in previously untreated pediatric patients with hemophilia A. Blood Adv. 2023;7(4):620-629. doi:10.1182/bloodadvances.2022007529
