Eptacog Beta Lowers Surgery Risk for Hem A Patients With Inhibitors
Eptacog beta was safe and 100% effective at preventing bleeds during and after minor surgeries in hemophilia A patients with inhibitors, according to data from a Phase 3 trial.
The treatment’s efficacy at managing bleeds dropped with major surgeries, with post-operative success seen in 66.7% of evaluated cases.
Overall, these findings support the potential of eptacog beta in helping to manage bleeds during and after surgery in hemophilia patients with inhibitors.
Trial results were reported in the study, “PERSEPT 3: A phase 3 clinical trial to evaluate the haemostatic efficacy of eptacog beta (recombinant human FVIIa) in perioperative care in subjects with haemophilia A or B with inhibitors,” published in the in the journal Haemophilia.
People with hemophilia have a deficiency in certain clotting factors — factor VIII (FVIII) in the case of hemophilia A and factor IX (FIX) in the case of hemophilia B — necessary to prevent excessive bleeding.
Replacement therapy, in which patients receive a version of the clotting factor they are missing, is a current standard of care for both types of hemophilia.
However, patients can develop inhibitors, or neutralizing antibodies, against these clotting factors that ultimately reduce the treatment’s effectiveness.
Eptacog beta is a bypassing agent designed to boost blood clotting in hemophilia patients with FVIII or FIX inhibitors. It was developed by the French company Laboratoire Francais du Fractionnement et des Biotechnologies (LFB).
The therapy was approved in the U.S., under the brand name Sevenfact, in April 2020 to treat and control bleeds in adults and adolescents, ages 12 and older, with hemophilia A or B with inhibitors.
A similar application is under review by the European Medicines Agency (EMA), with a decision expected by mid-2022.
These applications were supported by data from three completed, international and pivotal Phase 3 clinical trials: PERSEPT 1 (NCT02020369), PERSEPT 2 (NCT02448680), and PERSEPT 3 (NCT02548143).
PERSEPT 3 focused on the safety and efficacy of eptacog beta at treating bleeding episodes in boys and men with hemophilia A or B with inhibitors, who underwent surgery or other invasive procedures. Major surgical procedures are particularly challenging for hemophilia patients due to the heightened risk of post-operative bleeding.
An international group of researchers reported the main findings of PERSEPT 3 in this study.
In total, the trial enrolled 12 patients (mean age of 25; range of 2 to 56 years), all with severe hemophilia A. Eight patients were Caucasian and four were Black or African-American.
Six people undergoing major surgical procedures received eptacog beta intravenously, or directly into the vein, at a dose of 200 micrograms per kilogram (mcg/kg) of body weight just before surgery. The other six patients, having minor interventions like tooth extractions, were given the medication at a dose of 75 mcg/kg.
Following surgery, all continued with eptacog beta at a dose of 75 mcg/kg — for a minimum of five days in the case of major surgeries, and for at least two days after minor surgeries.
Treatment effectiveness was evaluated by surgeons or investigators using a four-point qualitative scale — excellent, good, moderate, or poor — reflecting blood loss during and after surgery. Post-surgery assessments were initially performed every day after the procedure and while eptacog beta was still being administered, and then every one or two days once the treatment had stopped.
The trial’s main goal was to assess the percentage of patients having a “good” or “excellent” postoperative outcome, corresponding to success cases, for either minor or major interventions, two days after the last infusion of eptacog beta. Cases whose outcomes were moderate or poor would be considered a failure.
Poor outcomes indicated uncontrolled bleeding, while moderate outcomes corresponded to a situation in which patients experienced blood loss that was substantially greater than expected for the procedure they had. Good or excellent outcomes corresponded to patients experiencing blood loss that was slightly higher, or that was similar or lower than expected.
During a surgery, all 12 patients were considered success cases, achieving good or excellent outcomes.
With a longer assessment, patients who underwent minor procedures achieved the primary success goal: all five evaluated after a last treatment were considered success cases. One person was not evaluated due to consent withdrawal.
Among those who underwent a major procedure, success was now reported in four of the six (66.7%) patients.
Overall, 81.8% of the procedures were considered a success, according to surgeon or investigator evaluations.
In the two failed major surgery cases, bleeding complications were not resolved with eptacog beta. One patient had undergone a total knee replacement, and the other a hip replacement surgery. Both discontinued the medication and received alternative treatments.
The hip replacement surgery patient died following an episode of acute severe anemia due to a gastrointestinal hemorrhage (blood loss). An analysis by the trial’s independent data monitoring committee found no evidence supporting an association with eptacog beta.
No cases of blood clot events or antibody development against eptacog beta were registered.
These findings suggest that eptacog beta is a well-tolerated agent for “bleed management in major and minor surgical procedures in paediatric and adult patients with haemophilia A or B with inhibitors,” the researchers wrote.
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