The study, “Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials,” was published in the journal Haemophilia.
Hemophilia A is caused by the lack of a functional blood clotting protein, called factor VIII (FVIII). Those with this disorder typically need treatment with FVIII concentrates to prevent bleeding during surgery.
Novo Nordisk‘s Esperoct is a recombinant (engineered) version of FVIII designed to remain active in the body for longer periods than the original FVIII. With a half-life — the time it takes for a compound’s levels to reduce by half in the body — up to 1.6 times longer than standard FVIII products, Esperoct requires less frequent dosing.
The Novo Nordisk-sponsored open-label Phase 3 trial, called pathfinder 3 (NCT01489111), assessed Esperoct in adults and adolescents with severe hemophilia A who were undergoing major surgery. Preliminary data coming from 16 patients ages 12 and older had already given shown that Esperoct was an effective and well-tolerated treatment to prevent and stop bleeds.
Scientists are now reporting the full pathfinder 3 results in 35 adults and adolescents, at a median age of 39, who underwent 49 major surgeries. Most (44) were orthopedic procedures, including 16 joint replacements and 11 arthroscopic interventions.
Results showed that Esperoct successfully prevented bleeding during surgery and in the postoperative period in 47 of 49 (95.9%) major surgeries. The therapy led to moderate responses in the remaining two procedures.
Median blood loss during surgery was 75 mL. Only four bleeds, all in joints, were reported after surgery, three of which were successfully treated with Esperoct (the fourth was not evaluated).
In addition, blood transfusions (11 in total) were only necessary in five of the procedures, either during surgery itself or up to six days after. Three of these four patients had an excellent or good response to Esperoct during surgery, except one patient (with a hip replacement) who had a moderate response.
After surgery, people stayed in hospital for approximately 10 days and less than a day in intensive care.
The mean number of injections per patient on the day of surgery was 1.7. Overall mean dose of Esperoct was 75.5 international units per kilogram of body weight (IU/kg).
During the first six days after surgery, patients took approximately 5.8 injections at a daily dose of 33 IU/kg. On days seven through 14 post-surgery, the number of injections was lowered to 4.5 and the daily dose to 20.3 IU/kg.
Compared with other standard products, Esperoct’s dose “was similar on the day of surgery, but the postoperative daily dose and frequency of injections was lower,“ the scientists wrote. This may ”decrease treatment burden whilst achieving desired therapeutic predose FVIII levels.”
In addition, FVIII activity levels before, during, and after surgery were within the levels recommended by the World Federation of Hemophilia.
Most adverse events during surgery and potentially related to Esperoct were mild or moderate and patients were able to recover. Only two serious adverse events in the same patient, bleeding and wound ischemia, were deemed possibly related to Esperoct.
The study also reported safety results in 23 children taking part in another Phase 3 trial called pathfinder 5 (NCT01731600), who underwent a total of 45 minor surgeries, mostly dental procedures. Children in this trial took regular Esperoct for prevention or an extra Esperoct dose before the procedure. No adverse events likely related to Esperoct were observed.
Pathfinder 5 and another previous Phase 3 trial, called pathfinder 2 (NCT01480180), both showed that Esperoct is safe and effective in preventing and treating bleeds in adults, adolescents and children with severe hemophilia A.
“The results from these completed trials provide further evidence for the haemostatic [prevent bleeding] efficacy and safety of [Esperoct] in the perioperative management and treatment of bleeds during major surgeries in adults/adolescents with haemophilia A,” the scientists wrote. “Also, turoctocog alfa pegol can be used to manage minor procedures successfully in children without safety complications.”
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