FROM HAEMOPHILIA
Some patients with severe hemophilia A can be managed with weekly injections of the recombinant factor VIII (rFVIII) product turoctocog alfa pegol (N8-GP), based on results from an extension of the pathfinder 2 trial.
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In patients who had two or fewer bleeding episodes during the preceding 6 months, N8-GP was effective for prophylaxis and treating bleeding episodes without causing inhibitor development, reported lead author Nicola Curry, MD, of the Oxford (England) Haemophilia and Thrombosis Centre at Churchill Hospital and her colleagues.
The trial exemplifies an ongoing effort to reduce frequency of prophylaxis in hemophilia A.
N8-GP, given every 4 days (or twice weekly in children), was approved by the Food and Drug Administration in February 2019; however, the investigators hypothesized that dose frequency could be stepped down in those who responded well to initial treatment.
“Many patients struggle to integrate prophylactic schedules into their daily lives, leading to missed injections and increased bleeding episodes,” the investigators wrote in a Haemophilia. “Therefore, prophylactic strategies offering effective haemostatic coverage with more convenient administration schedules are needed.”
To this end, the investigators identified 55 patients (at least 12 years old) from the pathfinder 2 trial who had two or fewer bleeding episodes during the preceding 6 months. From this group, 17 patients continued to receive 50 IU/kg of N8-GP every 4 days, as they had done during the main trial, while 38 patients received a higher dose – 75 IU/kg – every 7 days.
When necessary, N8-GP was used to treat bleeding episodes. Primary coendpoints were immunogenicity and efficacy, while all secondary endpoints were safety measures.
For both cohorts, median annualized bleeding rate (ABR) was 0.00 days, and greater than 50% of patients experienced no bleeds (53% every 4 days vs. 58% weekly). No inhibitors developed during the extension phase of the trial.
Along with strong support for weekly prophylaxis, N8-GP demonstrated efficiency in treating bleeding episodes; 87.5% of episodes were controlled with just one injection. This rate increased to 94.7% when including two or fewer injections.
During the study, 108 adverse events were reported in 65.5% of patients, although almost all were mild or moderate in severity, and unrelated to N8-GP. Five adverse events in five patients were related to treatment, including rash, headache, purpura, increased aspartate aminotransferase, and thrombocytopenia. No thromboembolic events were reported.
“These findings suggest that weekly N8-GP may provide effective prophylaxis with a reduced treatment burden for a selected subset of low-bleeding patients with severe haemophilia A,” the investigators wrote.
The study was funded by Novo Nordisk. The investigators reported financial relationships with Bayer, CSL, Novo Nordisk, Octapharma, Genentech, Shire, and others.
SOURCE: Curry N et al. Haemophilia. 2019 Feb 28. doi: 10.1111/hae.13712.