For patients with severe hemophilia A, N8-GP, an extended half-life recombinant factor VIII product, was safe and efficacious according to the results of the pathfinder clinical programs, presented at the Thrombosis & Hemostasis Summit of North America (THSNA) 2020 Virtual Conference.
The pathfinder trials were multicenter, multinational studies that evaluated the use of N8-GP for routine prophylaxis and bleed control in adolescent and adult patients (aged 12 years and older; pathfinder2) and pediatric patients (aged younger than 12 years; pathfinder5) with severe hemophilia A who were previously treated.
The current analysis aimed to compare the efficacy and safety of N8-GP in US vs global (including US) participants. In the pathfinder2 trial (ClinicalTrials.gov Identifier: NCT01480180), 177 adolescent and adults patients (mean age, 30.9 years) received N8-GP 50 IU/kg every 4 days as routine prophylaxis, and of those, 43 patients were from the US (mean age, 21.4 years). Additionally, 12 patients (mean age, 39.8 years) had received 20 IU/kg to 70 IU/kg as on-demand treatment, and 5 of those patients (mean age, 39.2 years) were from the US.
In the pathfinder 5 trial (ClinicalTrials.gov Identifier: NCT01731600), 68 pediatric patients (mean age, 6.0) received N8-GP 65 IU/kg twice weekly as routine prophylaxis and 20 IU/kg to 75 IU/kg as needed for bleed episodes. Of those patients, 21 (mean age, 5.4 years) were from the US.
Among adolescent and adult patients, 1270 bleeds, including 6 severe bleeds, in the 12 patients using on-demand N8-GP occurred during the treatment period, and 268 of these bleeds (and 1 severe bleed) were in the 5 US patients. The median annualized bleeding rate (ABR) was 31.03 in the global group and 30.22 in the US-only group.
In the adolescent and adult prophylaxis group, 1312 bleeds, including 22 severe bleeds (17 joint, 4 gastrointestinal, and 1 muscular), and 304 of these bleeds (4 severe) occurred in patients from the US. The median ABR was 0.99 in the global group and 0.86 in the US-only group.
Among the pediatric population, 330 bleeds, including 3 severe bleeds, in 55 patients occurred, and 81 of these bleeds (1 severe) were in 18 patients from the US. The median ABR was 0.81 in the global group and 0.76 in the US-only group.
In both studies the majority of hemostatic responses among the groups were considered excellent. In the global adolescent and adult study, 93% and 85% of bleeds in patients on the prophylaxis regimen and 97% and 85% of bleeds in patients on the on-demand regimen were successfully treated with 1 to 2 injections in the global group and US-only group, respectively. Similar hemostatic response were also seen in the pediatric study.
Adverse events (AEs) considered possibly or probably related to N8-GP, which included rash, redness, itching, and injection site reactions, occurred in 59 patients (13 US-based) and 11 patients (3 US-based) in the prophylaxis and on-demand regimens, respectively, in the pathfinder2 (adolescent and adult) study, and 16 (7 US-based) pediatric patients on the prophylaxis regimen had these treatment-related AEs in the pathfinder5 study.
“In conclusion, N8-GP was an effective and well-tolerated treatment in both adult and pediatric patients with severe hemophilia A in the analyses of both global and US participants in the pathfinder trials,” a study author said.
Disclosures: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Wheeler AP, Escobar M, Kearney S, et al. Efficacy and safety of N8-GP for prophylaxis and bleed control in US vs global patients with hemophilia A: results from the pathfinder clinical program. Abstract presented at: THSNA 2020 Thrombosis & Hemostasis Summit of North America; October 27-30, 2020. Abstract 64.