Long-term Preventive Use of Esperoct Effective in Hemophilia A
Long-term prophylactic (preventive) treatment with a fixed dose of Esperoct (turoctocog alfa pegol) — approved in the U.S. and the EU in 2019 — was effective in preventing and stopping bleeding in people with severe hemophilia A, according to data from two Phase 3 clinical trials.
Findings from the two studies also showed that, over a period of up to five years, there were fewer bleeds, and those reoccurred less frequently.
“Fixed-dose … prophylaxis demonstrated long-term efficacy in patients of all ages without the need for extensive monitoring and pharmacokinetic [what the body does to a drug] assessment,” the researchers wrote.
According to the team, these results show that simplified regimens can be effective without clinicians having to “resort to personalized prophylaxis where dose and dosing frequency are tailored to each patient’s needs.” In short, it lessens the need for “continual adjustments and regular laboratory testing,” the researchers wrote.
These findings were detailed in “Post-hoc analysis on the long-term response to fixed-dose prophylaxis with N8-GP in patients with haemophilia A,” a study published in the journal Haemophilia.
Hemophilia A is caused by the lack of clotting factor VIII (FVIII) — a protein that helps the blood clot. Treatment includes supplying patients with a version of FVIII to substitute for the one they are missing, using so-called replacement therapies.
Novo Nordisk’s Esperoct is an FVIII concentrate that is approved in many countries, including Canada, as a replacement therapy for patients with hemophilia A. It can be used as a preventive therapy to help prevent bleeds, or as an on-demand treatment to help stop a bleeding episode.
Its safety and efficacy were evaluated in a range of studies, including the Phase 3 trials Pathfinder 2 (NCT01480180) and Pathfinder 5 (NCT01731600). Pathfinder 2 enrolled 186 people with severe hemophilia A, ages 12 or older, while Pathfinder 5 involved 68 hemophilia A patients under 12.
Both showed that Esperoct was effective at treating severe hemophilia A, as well as in preventing or reducing the number of bleeds patients experienced. It also was found to ease some of the quality of life burdens among individuals with the blood disorder.
Now, researchers reported the findings of a new analysis of final data from both trials. Their goal was to determine how often bleeds reoccurred in a same location and how effective long-term preventive treatment was in reducing the annual bleeding rate (ABR). The team also sought to determine FVIII trough levels — corresponding to its levels in the bloodstream immediately before the next dose of Esperoct is administered — in patients receiving consistent preventive treatment.
All participants included in the analysis received a fixed dose of Esperoct. The medication was given at a dose of 50 international units per kilogram of body weight (IU/kg) every four days for adolescents and adults in the main phase of Pathfinder 2, and at 60 IU/kg twice weekly for children in Pathfinder 5.
In Pathfinder 2, 136 patients were exposed to Esperoct for 600 days (about 20 months) or longer. Of these, 117 (86%) experienced bleeding episodes and 22 (16.2%) experienced a reoccurring bleed, meaning they had two or more bleeds in the same location within a two-week time window.
Bleed reoccurrence decreased over time. However, bleeding risk generally increased as the time since the last dose increased.
For the 177 patients who received preventive treatment at some point during the trial, practically all (99%) had reoccurring bleeds in the joints.
Among the 61 patients who received consistent preventive treatment over the course of Pathfinder 2, mean ABR decreased from 3.5 bleeds per year (year one) to 1.6 bleeds per year (year six). Mean FVIII trough levels stabilized at around 5% at year six.
In Pathfinder 5, 63 patients were exposed to Esperoct for 600 days or longer. Of these, 57 (90.5%) experienced at least one bleed, and 12 (19%) a reoccurring bleed. A total of 426 bleeds were observed, of which 15 (3.5%) were reoccurring.
Similar to what was observed in Pathfinder 2, bleed frequency in Pathfinder 5 decreased over time. However, in the last part of the main phase of the study, mean ABR increased. According to researchers, this occurred in part due to bleeds in six patients who had been exposed for a small number of days (less than 40) to Esperoct. Mean FVIII trough levels stabilized at about 4% at year five in patients receiving consistent preventive treatment in Pathfinder 5.
“The data reported here support the initiation of patients in a fixed-dose prophylaxis regimen with possible adjustments to treatment based on clinical response,” the researchers concluded.