Prasugrel hydrochloride for the treatment of sickle cell disease

ABSTRACT

Introduction: Therapeutic options for sickle cell disease (SCD) are limited and, currently, only one drug (hydroxyurea) has FDA approval for the treatment of adult SCD. While this genetic disease is caused by hemoglobin polymerization, subsequent downstream events trigger platelet activation, vaso-occlusion and the disease’s complex pathophysiology.

Areas covered: The oral thienopyridine, prasugrel hydrochloride, irreversibly inhibits the P2Y12 receptors, inhibiting ADP-dependent platelet activation. We discuss recent clinical trials evaluating the pharmokinetics of prasugrel and its potential for use in SCD.

Expert opinion: Prasugrel administration in SCD appears to be well tolerated and safe. However, although this drug modestly inhibits platelet activity in these patients, administration of prasugrel to a large group of children and adolescents for up to 24 months failed to convincingly reduce vaso-occlusive complications. Speculatively, prasugrel may be of occasional use for off-license purposes in patients unable or unwilling to take hydroxyurea (particularly in 12–17-year olds). Although there is currently no prospect of prasugrel being licensed for use in SCD, the success of on-going trials of other antiplatelet agents in SCD might lead to further trials of prasugrel in SCD.

KEYWORDS:

• Pain
• platelets
• purinergic receptors
• sickle cell disease
• vaso-occlusive events

Declaration of interest

D. Rees was an investigator on the DOVE study of prasugrel in children with sickle cell disease, and has received funding from Eli Lilly as an investigator on clinical trials as well as for attending conferences and scientific meetings. N. Conran receives research funding from Bayer, for matters unrelated to Prasugrel. 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.

Additional information

Funding

David Rees and Nicola Conran form part of a cooperation between Kings College London and the University of Campinas, supported by the Institutional Links Program funded by the Newton Fund and CAPES-Brazil.