An update of the current pharmacotherapeutic armamentarium for hemophilia A

ABSTRACT

Introduction

For several decades, we have seen unprecedented advances in novel therapy development for hemophilia A. These advances address the unmet need of replacement therapy, and they include the development of recombinant products with improved pharmacokinetics, subcutaneously administered products, and those with better efficacy and safety profiles in hemophilia A management.

Areas covered

In this update of hemophilia A treatment, the author summarizes data from completed standard half-life FVIII products, extended half-life FVIII products and FVIII mimetic studies. All products have an acceptable safety profile. The standard half-life products, EHL-FVIII products and emicizumab are efficacious in the prevention and treatment of bleeds and for EHL-FVIII in the perisurgical setting.

Expert opinion

Advances in pharmacotherapy for hemophilia A have been characterized by changing care goals from supportive care to eliminating infections, preventing inhibitors, and more recently achieving zero bleeds in many patients. While gene therapy has the potential for functional cure in hemophilia A, it has many limitations which need to be addressed. Therefore, pharmacotherapy is likely to remain the mainstay in the management of hemophilia A and promises to get better with currently available therapies. Evolving factor and non-factor replacement therapies may also improve current unmet needs in hemophilia A management

KEYWORDS:

• rFVIII
• standard half-life FVIII
• extended half-life FVIII
• hemophilia A
• pharmacotherapy
• emicizumab

Article highlights

• Replacement therapy is the widely accepted standard of care in haemophilia management

• Recently developed novel standard half-life FVIII products were developed to address immunogenicity challenges, increase access and to improve efficacy of management of haemophilia A patient

• Extended half-life products evolved to facilitate the implementation of prophylaxis as the new standard of for people with haemophilia.

• Several subcutaneously administered FVIII mimetics were developed to reduce the treatment burden and to optimize prophylaxis in haemophilia care

• Development of non-factor therapies is advancing with several of these molecules in phase 2/3 of their development, however, thrombosis remains concern with these agents

• Several gene therapy programs are currently ongoing in haemophilia with the most advanced studies indicating that AAV mediated therapy may provide functional cure for people with haemophilia A.

This box summarizes key points contained in the article.

Declaration of interest

The author has no 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

One reviewer is a full-time employee of Takeda, and a stock owner of Takeda. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This manuscript has not been funded.