The availability of new drugs for hemophilia treatment

ABSTRACT

Introduction

A number of new FVIII/IX concentrates enriched the portfolio of products available for the treatment of hemophilia A/B patients. Due to the large inter-patient variability, accurate tailoring of the therapy became essential to improve patients’ adherence, clinical outcomes, and cost/effectiveness ratio. Recently, non-replacement therapies have taken the limelight and succeeded in decreasing the bleedings of patients.

Areas covered

The PK characteristics, efficacy, and safety of the new rFVIII and rFIX concentrates and of non-replacement therapy, are reported in detail in the published clinical trials

Expert opinion

Outstanding improvements of rFIX concentrates’ pharmacokinetics and pharmacodynamics have allowed to reduce the bleedings in hemophilia B patients, in order to increase their adherence to prophylaxis and quality of life. Less significant are the effects of pegylation or Fc fusion on the pharmacokinetics of the new rFVIII concentrates. The new non-replacement therapy is achieving the favor of many treaters and patients, in particular those with Factor VIII inhibitors. Great attention must be paid to the dangerous synergy of APCC and emicizumab, responsible for some fatal events during the clinical trials and compassionate use of this drug. So far, replacement therapy should be the standard of care for hemophilia patients without inhibitors or difficulties in venous access.

KEYWORDS:

• Concizumab
• emicizumab
• fitusiran
• hemophilia A/B
• rFIX EHL
• rFVIII EHL

Article highlights

• Pegylation or fusion with Fc improved the half-life of new rFVIII EHL concentrates

• The new rFIX EHL concentrates scored a significant improvement of the FIX half-life by pegylation or fusion with Albumin or Fc

• So far, the immunogenicity of rFVIII EHL concentrates seems to be a severe side effect of replacement therapy

• The new non-factor-replacement therapy deserves a lot of attention from medical doctors

• The attempts to reduce the weight of natural anticoagulants (TFPI or Antithrombin) to improve the hemostatic balance of hemophilia A patients reported preliminary severe adverse events (thrombosis)

• The recombinant humanized Mab (Emicizumab) miming FVIII:Ca achieved very good outcomes during prophylaxis of bleedings but the association with APCC for treatment of the overt bleedings resulted in fatal episodes of thrombosis

Declaration of interest

The authors have 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

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

Additional information

Funding

This paper was not funded.