Investigational drugs for immune thrombocytopenia

ABSTRACT

Introduction

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease of unknown cause. Autoantibodies, self-reactive T cells and other immune abnormalities, with impairment of platelet production, lead to a reduced platelet count. Until recently, therapy was largely empirical using immune suppressants (none of which have undergone randomized clinical trials). These therapies have variable efficacy and are associated with predictable unwanted effects which impact patient quality-of-life. With greater understanding of the underlying pathophysiology, better, more targeted therapies have been developed; however, there is still an urgent need for additional classes of treatment.

Areas covered

This article covers new TPO receptor agonists, Syk inhibitors, Fcγ receptor antagonists, BTK and complement inhibitors, and other therapies. Insights into the most promising therapies are offered. Novel ITP treatments currently in clinical trials and those recently approved come under the spotlight.

Expert opinion

Thrombopoietin receptor agonists remain the most effective treatment for ITP and have changed the ITP therapeutic landscape remarkably. Other new molecules such as Fcγ receptor blockers, Bruton tyrosine kinase, complement inhibitors, and others are unlikely to enjoy the same success rate as the TPO-RAs, but nonetheless they will find a place in the management of patients with ITP.

KEYWORDS:

• Immune thrombocytopenia
• neonatal fc receptor
• Bruton tyrosine kinase
• complement inhibitor
• TPO-R agonist

Article highlights

• Until recently there were few therapies developed specifically for ITP; older therapies, especially corticosteroids and immune suppression, have many unwanted effects which lead to an increased morbidity and mortality for patients with ITP

• The current focus in ITP management is on quality of life rather than arbitrary platelet counts. Current approved therapies work well and improve the quality of life for patients with ITP

• The second-generation thrombopoietin receptor agonists were launched in 2008 and were the first approved therapies for this disorder

• Better understanding of the underlying pathophysiology has led to better, more targeted therapies including antagonists of the neonatal Fc receptor, Bruton tyrosine kinase, complement, and others

• The anti-FcRn class appears promising, and these are likely to find a place in the management of ITP patients who have failed TPO-RAs, the contemporary second-line class of treatment

• BTK inhibitors and anti-complement therapies have limited data at present. The exact placement of these at present is unclear. It is our opinion that they will likely be used after a patient has received an anti-FcRn

• When we understand the principal mechanism causing each patient’s ITP we will be able to offer specific therapy targeting the pathophysiology. Currently, this is not possible

This box summarizes key points contained in the article.

Declaration of interest

Drew Provan has received research support and honoraria from Amgen, Novartis, SOBI, UCB, argenx, Rigel and Chugai and has acted as a consultant for UCB, argenx, MedImmune, and Ono; he also serves on a DSMB for an investigator-led study of rituximab in ITP and has received a basic shares package from previous employment by GlaxoSmithKline.

Adrian C. Newland is consultant for Amgen, Angle, argenx, Dova, Novartis, Ono, Rigel, and Shionogi; received funding from Amgen, Novartis, and Rigel; received honoraria directly from Amgen, Angle, argenx, Dova, Novartis, Ono, Rigel, and Shionogi; and paid expert testimony from argenx and Rigel.

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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One reviewer received grants from Novartis and Amgen. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.