FEIBA (factor eight inhibitor bypassing activity), also known as activated prothrombin complex concentrate, is a bypassing agent approved for use in patients with hemophilia type A and type B. Nearly 30% of these patients stop responding to replacement therapy with factors VIII (for type A patients) or IX (type B), because of the development of inhibitors against these factors.

In use since 1975, FEIBA prevents blood loss during surgery and is taken as a routine prophylactic agent to reduce the frequency of bleeding episodes. It is not indicated for the treatment of bleeding episodes in hemophilia patients who do not have inhibitors against factors VIII and IX.

FEIBA is a trademark of Baxalta, which is now wholly owned by Takeda.

How does FEIBA work?

FEIBA contains multiple components that are required for blood clotting. These include non-activated factors II, IX, and X, proteins that make up the prothrombin complex, and active factor VII.

When transfused into hemophilia A and B patients who have stopped responding to replacement therapy because they developed inhibitors against either factor VIII or IX, FEIBA successfully induces clotting to stop bleeding episodes.

FEIBA in clinical trials

The results of a double-blind clinical trial, which were published in the New England Journal of Medicine, reported the effect of FEIBA on joint and muscle bleeding in hemophilia A patients with inhibitors against factor VIII. During the trial, 15 patients received either FEIBA or a control preparation containing only a non-activated prothrombin-complex concentrate for 150 bleeding episodes (four mucocutaneous bleeding, 117 joint bleeding, and 29 muscle bleeding) over a 15-month period. The control preparation was found to be effective in 52% of the episodes, while FEIBA was found to be effective in 64% of the episodes. The researchers said that FEIBA was significantly better than the control preparation in stopping bleeding at the joint or muscle, and in improving joint mobility.

Another study published in the journal Blood reported the effects of FEIBA in achieving hemostasis in 46 patients with factor VIII inhibitors and three patients with factor IX inhibitors. FEIBA was used for 165 bleeding episodes (102 in the joints, 20 in mucous membranes, 33 in the muscles and soft tissues, and 10 emergency episodes that included three in the central nervous system and four occurring during surgical procedures). The study showed that 93% of the bleeding episodes were controlled with one or more infusions.

A total of 34 hemophilia A patients with high-titer inhibitors were included in a Phase 2/3 prospective, randomized, crossover study (NCT00221195) to study the effect of prophylactic infusion versus on-demand treatment with FEIBA for six months. Patients took the prophylactic treatment three times a week for the first six months then switched to on-demand treatment for bleeding episodes for six months. The two treatment periods were separated by a three-month washout period. Twenty-six of the 34 patients completed both treatment periods.

The results of the study showed that compared with on-demand therapy, prophylaxis treatment reduced bleeding episodes by 62% and target-joint bleeding by 72%. This study also showed that prophylactic use of FEIBA was safe and effective in decreasing joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors.

In a Phase 3 prospective study (NCT00851721), 17 patients were treated prophylactically with FEIBA while 19 patients were treated on demand over one year to evaluate whether prophylaxis treatment was a safe and effective option. A statistically significant 72.5% reduction in the median annualized bleeding rate was observed during prophylaxis compared to on-demand treatment. Three patients (17.6% of all patients) on prophylaxis experienced no bleeding episodes compared to none in the on-demand group. On-demand treatment required a significantly higher use of FEIBA to treat bleeding episodes compared to prophylaxis treatment. No differences were found in the rates of related adverse events between the two treatments.

A prospective, non-interventional, observational multi-center cohort study called the FEIBA global outcome study (FEIBA-GO) is underway to capture long-term outcomes on the effectiveness, safety, and quality of life in 51 people with hemophilia with inhibitors. The primary objective of the study is to describe the hemostatic effectiveness of FEIBA in different settings, such as prophylaxis and on-demand, including in patients on immune-tolerance induction. Secondary objectives include joint functionality outcomes, safety, health-related quality of life, daily activity levels, acute and chronic pain associated with hemophilia, and healthcare resources used.

Preliminary findings from the study, published in the journal Blood in December 2017, showed that at six months, prophylactic treatment with FEIBA can prevent joint bleeding in a way similar to that reported in patients without inhibitors on replacement prophylaxis. An updated interim report published in November 2019 stated that FEIBA continued to show safety and efficacy in an analysis of patients with more than 18 months’ follow-up.

A Phase 3, prospective, multi-center, open-label, randomized crossover study (NCT02764489) called FEIBA STAR is currently recruiting an estimated 32 adult participants in Croatia, Ukraine, and North Macedonia to evaluate the safety and tolerability of FEIBA when reconstituted in regular volume and 50% reduced volume, and with faster infusion rates in hemophilia A or B patients with inhibitors. This study is expected to be completed in March 2021.

A Phase 4 trial (NCT04205175) is investigating the safest dose range of FEIBA in hemophilia A patients who are already on Hemlibra (emicizumab). Results from a different clinical trial showed that patients who received both Hemlibra and FEIBA experienced cases of thrombotic microangiopathy. Because of these previous results, this current study is investigating the effects of single low doses of FEIBA on thrombin levels in the blood. The study is not yet recruiting but aims to recruit approximately 20 patients.

Other information

FEIBA is associated with an increased risk of thromboembolic events that cause stroke, blockage of the main blood vessel to the lungs, deep vein blood clots, and allergic reactions in some patients.

Other common side effects during prophylactic use are low red blood cell counts, bleeding into a joint, diarrhea, nausea, and vomiting.

 

Last updated: Feb. 17, 2020

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