Safety evaluation of emicizumab prophylaxis in individuals with haemophilia A

ABSTRACT

Introduction

Emicizumab is a bispecific-humanized monoclonal antibody that improves hemostasis by bridging activated factor IX and factor X to substitute for the function of missing activated FVIII. It is an alternative to prophylaxis with factor VIII replacement and is associated with improved outcomes in individuals with hemophilia A with and without inhibitors.

Areas covered

Emicizumab is efficacious in reducing bleeding events when compared to on-demand treatment and factor-based prophylaxis. Except for the few thrombotic microangiopathy and thrombotic event cases mainly seen in the HAVEN 1 trial, emicizumab has an overall excellent safety profile with minimal side effects.

Expert opinion

Knowledge gaps include the efficacy and safety of emicizumab in younger age groups and those with mild or moderate hemophilia A. Future directions for research include exploring the risk of inhibitor recurrence in patients with a history of high titer inhibitor who have been successfully tolerized, who switch from factor prophylaxis to emicizumab, as well as conducting ‘real world studies’ to evaluate the patient’s perception of emicizumab in regard to ease and tolerability in order to optimize individualized treatment plans.

KEYWORDS:

• Emicizumab
• hemophilia A
• monoclonal antibody
• factor
• prophylaxis

Declaration of interest

C Thornburg has disclosed that she has received consulting fees from BioMarin, Bluebird Bio, Cyclerion, Genentech/Roche, Novo Nordisk, Sanofi Genzyme, Spark, and funds for research support from Bayer, Biomarin, NovoNordisk and Sanofi Genzyme.

G Young has disclosed that he has received consulting fees from BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure and funds for research support from Genentech/Roche, Grifols, and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Company review

Roche conducted a courtesy review for accuracy only at the request of the journal editor, and any comments were addressed at authors’ discretion.

Abbreviation key

HA – hemophilia A

HB – hemophilia B

HIV – human immunodeficiency virus

EHL – extended half-life

BPA – bypassing agents

aPCC – activated prothrombin complex concentrate

rFVIIa – recombinant activated factor VII

FVIIIa – activated factor VIII

ABR – annualized bleeding rate

Haem-A-QoL – Haemophilia Quality of Life Questionnaire for Adults

AE – adverse events

SAE – serious adverse events

ISR – injection site reactions

TE – thrombotic events

TMA – thrombotic microangiopathy

ADA – anti-drug antibody

ITI – immune tolerance induction

LMWH – low molecular weight heparin

ELISA – enzyme-linked immunosorbent assay

FAERS – FDA Adverse Event Reporting System

AHA – acquired hemophilia

Drug summary box

Table

Additional information

Funding

This paper was not funded.