Emicizumab: Review of the literature and critical appraisal

Abstract

Introduction Emicizumab‐kywh (ACE910) is a recombinant, humanized, asymmetric bispecific antibody that functions to bring activated FIX (FIXa) and zymogen FX into an appropriate steric conformation to medicate the activation of FX to FXa thereby mimicking the cofactor function of FVIIIa. Aim The objective of this manuscript was to review the development and potential role for emicizumab in the treatment of patients with haemophilia A with and without inhibitors. Methods A Cochrane Library and PubMed (MEDLINE) search focusing on emicizumab in haemophilia was conducted. Results In total, 37 citations were retrieved and serve as the database for the literature reviewed herein. Once‐weekly subcutaneous injection of emicizumab at three dose levels has been shown to be effective as prophylaxis to prevent bleeding in a majority haemophilia A patients with inhibitors to FVIII. Likewise, prevention of bleeding was also observed in more than two thirds of patients without inhibitors to FVIII. One antidrug antibody to emicizumab has been reported in over 600 treated patients, two have developed thromboembolic events and three thrombotic microangiopathy. These thrombotic complications have occurred in conjunction with FVIII‐bypassing agents, and none have been observed following recommendations from the manufacturer regarding concomitant use of bypassing agents. The median annual treated bleeding rates were decreased in patients with as well as those without an inhibitor to FVIII. Conclusion The principal advantage of emicizumab is subcutaneous administration and effectiveness irrespective of the presence of inhibitors. Emicizumab could conceivably represent a new epoch in the treatment of people with haemophilia A.

The societal burden of haemophilia A. I – A snapshot of haemophilia A in Australia and beyond

“…Studies undertaken internationally of the lifetime risk (ie the cumulative incidence) show that inhibitors will develop in 25%‐30% of people with severe HA compared with 5%‐12% of those with mild or moderate HA (Table 2). 7‐11 Patients who develop inhibitors typically do so soon after exposure to exogenous FVIII (eg within the first 20 exposure days to FVIII) and often early in the first 2‐3 years of life 6,8,12‐14 . However, recent evidence from the UK suggests that there is a second peak of patients with inhibitors observed in people with severe haemophilia aged over 60 years 15 …”

Emicizumab treatment: Impact on coagulation tests and biological monitoring of haemostasis according to clinical situations (BIMHO group proposals)

“…In the event of unusual bleeding symptoms, it is worthwhile measuring the plasma activity of emicizumab in order to determine the presence of anti-emicizumab neutralising antibodies (anti-drug antibodies, ADA), since rare cases have been described 6,8 or to demonstrate poor treatment compliance and adherence (Figure 4). 25 In such situations, although aPTT is sensitive to low emicizumab concentrations, 26 substantial prolongation of aPTT may be detected and emicizumab plasma activity may be below the usual plasma concentrations at the steady state (30-80 µg/mL).…”

“…week gives rise to a significant improvement in quality of life in patients for whom prophylaxis previously required intravenous infusion of FVIII concentrates 2-3 times per week. 6 9 and to know how to interpret these tests in patients receiving emicizumab in these situations. 10 National proposals for laboratory monitoring of patients treated with emicizumab are described according to different clinical situations.…”

Long‐term analysis of the benefit of prophylaxis for adult patients with severe or moderate haemophilia A

“…7,31,38 These data, which the present report may contribute to, will help to improve HA therapy and the quality of life of patients with HA. 22 Beside non-factor treatment options such as emicizumab, 39 prophylaxis with FVIII concentrates is still widely used to provide prophylaxis and treat HA patients to attain low ABRs or even a bleed-free life.…”