Unmet needs

In a study, 75% of ITP patients felt their condition was not well-managed from a HRQoL perspective.³

Current treatment goals in ITP are to stop active bleeding and reduce the risk of further bleeding. Response rates for ITP treatments vary widely as measured by improved platelet counts, and the mechanisms of action (MOA) of current treatments may not fully address the complex nature of the disease.¹

Additional rescue medication is often necessary for patients with ITP.⁴

Investigational therapies for ITP

Ongoing research aims to better address the multiple dimensions of ITP by targeting the underlying pathophysiology of the disease. Several clinical trials are in progress investigating novel drugs for treating ITP.^5,6

Bruton’s tyrosine kinase (BTK) inhibitors^5,7-9

BTK is an enzyme expressed mainly in B cells, myeloid cells, and platelets. BTK is crucial for the signalling pathways that regulate the development and maturation of B cells and the overall immune response.

Several BTK inhibitors targeting these mechanisms have been approved or are currently in development. BTK inhibitor (BTKi) therapy can prevent macrophage phagocytosis in ITP, leading to a decrease in platelet destruction; can prevent production of autoantibodies; and may also inhibit inflammation.

However, patients can develop a resistance to BTK inhibitors when mutations in the targeted cell occur. Newer generations of BTK inhibitors aim to tackle BTK inhibitor resistance and common class AEs with various strategies. 

Neonatal Fc receptor (FcRn) blockers^5,10

FcRn regulates the immune response by presenting immunoglobulin G (IgG) antigens to immune cells and regulating IgG levels in the plasma.

FcRn blockers in ITP may increase platelet antibody clearance, leading to a decrease in peripheral platelet destruction and immune response. 

Recombinant immunoglobulin multimers⁶

Recombinant immunoglobulin multimers decrease platelet destruction and increase antiplatelet antibody clearance. Recombinant immunoglobulin multimers bind to Fc receptors on immune cells, preventing the attachment of pathogenic antibodies to these receptors. As a consequence, in conditions like ITP, the immune-mediated destruction of platelets could be reduced and platelet counts increase.

Complement inhibitors^6,11

Complement inhibitors decrease complement-dependent cytotoxicity. Complement inhibitors block the activation of the complement system, a part of the immune response that marks cells, such as platelets, for destruction. By inhibiting specific complement pathways, these agents may potentially reduce platelet destruction in autoimmune conditions like ITP. 

Plasma-cell–depleting therapies^6,11

Plasma-cell–depleting therapies decrease antiplatelet antibodies. Plasma-cell–depleting therapies target and reduce plasma cells, helping to minimise platelet destruction and improve platelet counts. However, plasma-cell–depleting therapies may fail to completely eliminate long-lived plasma cells that regulate antiplatelet autoantibody production. 

B cell activating factor (BAFF) inhibitors^12,13

BAFF binds to its receptor on B cells promoting the survival of B cells and initiating the differentiation of the B cells to immunoglobulin-producing plasma cells. Both are crucial factors in ITP pathogenesis.

BAFF inhibitors may reduce B cell survival and consequently decrease antiplatelet antibodies. Thus, in conditions like ITP, BAFF inhibitors could help to preserve platelet counts.

TPO-RA, thrombopoietin receptor agonist.