Emerging drugs for hemophilia A: insights into phase II and III clinical trials

ABSTRACT

Introduction

Hemophilia is a lifelong, genetic-bleeding disorder, which inadequately treated results in permanent joint damage. It is characterized by spontaneous and trauma-related bleeding episodes. In the last 50 years, treatment has seen dramatic improvements which have improved the quality of life of persons with hemophilia.

Areas covered

This review will provide a summary of current pharmacological approaches for hemophilia A as well as discuss novel agents which are either approved recently or in phase II–III clinical trials, plasma-derived and recombinant factor VIII (FVIII) products, extended half-life FVIII products, bypassing agents and non-replacement therapies.

Expert opinion

Novel therapies are already changing the way that hemophilia A is managed, and as more new therapies get approved, there will be a revolution in the management of this serious condition. Clinicians will have both the opportunities as well as the challenges of incorporating such new technologies into clinical practice.

KEYWORDS:

• Bleeding disorders
• hemophilia
• inhibitors
• gene therapy
• extended half-life products
• non-replacement therapies

Funding

This paper was not funded.

Abbreviation table

FVIII	=	Factor VIII
PWH	=	Patients with hemophilia A
HCV	=	Hepatitis C virus
HIV	=	Human immunodeficiency virus
pdFVIII	=	Plasma derived FVIII
rFVIII	=	Recombinant FVIII
PUP	=	Previously untreated patients
QOL	=	Quality of life
BPA	=	Bypassing agents
aPCC	=	Activated prothrombin complex concentrate
rFVIIa	=	Activated recombinant factor VII
VWF	=	von Willebrand factor
ITI	=	Immune tolerance induction
BDD	=	B-domain deletion
CVV	=	Central venous catheter
EHL FVIII	=	Extended half-life FVIII
SHL FVIII	=	Standard half-life FVIII
FDA	=	Food and Drug Administration
EMA	=	European Medicines Agency
ABR	=	Annualized bleeding rate
siRNA	=	Small interfering RNA
AAV	=	Adeno-associated virus
PLC	=	Human placental cells

Declaration of interest

G Young has received consulting fees and honoraria from BioMarin, Bioverativ/Sanofi, CSL Behring, Freeline, Genentech/Roche, Grifols, Novo Nordisk, Spark, Takeda, and UniQure and research grants from Grifols, Genentech 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 apart from those disclosed.