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Summary Primary immune thrombocytopenia (ITP) is an antiplatelet‐antibody‐mediated disorder with accelerated platelet clearance and decreased platelet production. Rozanolixizumab, a monoclonal IgG4 anti‐FcRn antibody, blocks IgG recycling and decreases IgG levels. We report efficacy and safety of rozanolixizumab in adults with persistent/chronic ITP in 24‐week phase 3 studies (TP0003; TP0006), and their 52‐week open‐label extension (OLE). Primary end‐point was durable clinically meaningful platelet response (DCMPR) of ≥50 × 109/L for 8/12 weeks during Weeks 13–25 in the double‐blind studies. Operational delays and evolving ITP treatment landscape led the sponsor to terminate these studies early; thus, only 21 and 12 (TP0003) and 20 and 10 (TP0006) patients were randomised to rozanolixizumab or placebo. Forty‐three patients enrolled in the OLE: 42 started on every 2‐week dosing; 21 later switched to weekly dosing. More rozanolixizumab‐treated than placebo‐treated patients achieved DCMPR: 4/21 versus 0 (TP0003) and 1/20 versus 0 (TP0006). Platelet increases to ≥50 × 109/L were observed on Day 8 in 52.4% (TP0003; 2/12 placebo) and 45.0% (TP0006; 1/10 placebo) of rozanolixizumab‐treated patients. OLE platelet increases were maintained while on weekly dosing. The most frequent treatment‐emergent adverse events overall were headache, pyrexia and nausea, as seen previously. Weekly dosing appears more efficacious than every 2‐week dosing. [ABSTRACT FROM AUTHOR]

Current therapies for immune thrombocytopenia (ITP) are successful in providing a haemostatic platelet count in over two-thirds of patients. Still, some patients have an inadequate response and there is a need for other therapies. A number of novel therapies for ITP are currently being developed based upon the current pathophysiology of ITP. Many therapies are targetted at reducing platelet destruction by decreasing anti-platelet antibody production by immunosuppression with monoclonal antibodies targetted against CD40, CD38 and the immunoproteasome or physically reducing the anti-platelet antibody concentration by inhibition of the neonatal Fc receptor. Others target the phagocytic system by inhibiting FcγR function with staphylococcal protein A, hypersialylated IgG, polymeric Fc fragments, or Bruton kinase. With a recognition that platelet destruction is also mediated by complement, inhibitors of C1s are also being tested. Inhibition of platelet desialylation may also play a role. Other novel therapies promote platelet production with new oral thrombopoietin receptor agonists or the use of low-level laser light to improve mitochondrial activity and prevent megakaryocyte apoptosis. This review will focus on these novel mechanisms for treating ITP and assess the status of treatments currently under development. Successful new treatments for ITP might also provide a pathway to treat other autoimmune disorders., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)