Investigational drugs to treat hemophilia

ABSTRACT

Introduction

Hemophilia A and B are congenital bleeding disorders. The current standard management of patients with severe hemophilia is prophylaxis which is given intravenously two or three times weekly; however, this is associated with a significant burden on the quality of life of the patient. The main attempts to improve the management of hemophilia is hence through the development of a new generation of products with properties facilitating prophylaxis and/or a better control of bleeding.

Areas covered

This review describes the preclinical and phase 1/2 studies investigating the innovative products for the management of hemophilia patients with or without coagulation factor inhibitors.

Expert opinion

Numerous innovative therapeutics, including factor concentrates and non-clotting factor-based therapies with extended half-life, are under clinical investigation. Among replacement therapies for hemophilia A, the results from phase 1/2 studies indicate that the most interesting products are those bioengineered using XTEN fusion technology. The anti-tissue factor pathway inhibitor antibody concizumab is the most innovative and interesting agent among non-clotting factor products. If the results of ongoing trials confirm the preliminary positive results, these promising agents will provide further improvements in the management and quality of life of patients with hemophilia.

KEYWORDS:

• Hemophilia
• bleeding disorders
• novel hemostatics products
• concizumab
• XTEN fusion technology
• clinical trial
• therapy
• emicizumab

Article highlights

• Hemophilia is a rare inherited bleeding disorder: the severity of its clinical phenotype is correlated with the residual level of the deficient coagulation factor.

• Replacement of the missing coagulation factor is the mainstay of treatment of hemophilia A and B.

• Numerous innovative therapies have been developed to overcome the drawbacks of the current treatment of hemophilia.

• Promising recombinant clotting factor products with extended half-lives are under clinical development.

• Among replacement therapies for hemophilia A, FVIII products bioengineered using XTEN fusion technology are the most interesting.

• Drugs targeting tissue factor pathway inhibitor, particularly concizumab, are currently being investigated in phase 1/2 studies with encouraging preliminary results.

• Innovative hemostatic agents have the potential to improve the management of hemophilia patients with and without inhibitors.

This box summarizes key points contained in the article.

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.