The FDA approved Rigel Pharmaceuticals' first-in-class SYK inhibitor fostamatinib for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

ITP is a rare disease in which the immune system attacks and destroys the body's own blood platelets. Current treatment options for ITP include steroids, splenectomy, thrombopoietin receptor agonists and more. But not all patients have an adequate response to these existing therapies.

SYK has a key role in the adaptive immune system, mediating immunoreceptor signalling in macrophages, neutrophils, mast cells and B cells. In ITP, inhibition of SYK with fostamatinib reduced antibody-mediated destruction of platelets in clinical trials, leading to platelet stabilization in 16–18% of patients, compared with 0–4% of patients receiving placebo. Serious adverse drug reactions included febrile neutropenia, diarrhoea, pneumonia and hypertensive crisis.

Drug developers once had bigger plans for this drug class. Rigel licensed the drug to AstraZeneca in 2010 for development and commercialization in rheumatoid arthritis and haematological malignancies, potentially much more profitable indications. AstraZeneca advanced it into phase III rheumatoid arthritis trials that same year, but then discontinued all development in 2013 and returned rights to Rigel “due to safety and efficacy reasons”. Investigators recently revisited these failed trials, and found that translational biomarker assessments may have been able to predict the results ahead of time.

A few other companies, including Gilead Sciences and Takeda Pharmaceuticals, are still persevering with SYK inhibitors in phase I/II oncology trials.