The European Medicines Agency (EMA) has recommended granting marketing authorization for rilzabrutinib (Wayrilz, Sanofi) to treat immune thrombocytopenia (ITP) in adults who are refractory to other medications. 

ITP is a rare acquired autoimmune disorder in which autoantibody-mediated platelet destruction and impaired platelet production result in thrombocytopenia and an increased risk of bleeding complications. Platelet counts may drop from normal levels of 150-400 10⁹/L to 5 10⁹/L or below.

First-line treatment of ITP is with corticosteroids, but frequently this is insufficient and up to three-quarters of patients relapse within 3-4 months, imposing significant healthcare costs for rescue therapies, hospital admission, and surgery to manage bleeding events.

Rilzabrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor that offers multi-immune modulation by inhibiting B cell activation, interrupting FcγR mediated phagocytosis, and potentially ameliorating the chronic inflammation associated with ITP.

The EMA said its benefits included a significantly higher rate of durable platelet response compared with placebo, especially when used in combination with corticosteroids and/or thrombopoietin receptor agonists. This had been shown in a phase 3 multi-center, randomized, double-blind, placebo-controlled study.

The most common side effects include diarrhea, nausea, headache, increased vulnerability to infections, abdominal pain, arthralgia, and nasopharyngitis. Hepatotoxicity may occur and drug interactions are common; prescribers should avoid co-administration with CYP3A inhibitors or inducers and with proton pump inhibitors.

The EMA stressed that treatment should be initiated and remain under the supervision of physicians experienced in the treatment of hematological diseases.

ITP may develop following viral infection, vaccination, or certain medications, but in most people the cause is unknown. It is an acute, self-limiting illness that resolves in 3-12 months in around 80% of children, whereas more than half of adults develop a chronic form that imparts a permanent risk of bleeding and bruising. There is an increased risk of ITP among people with other autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren syndrome.

Prevalence varies by country but annual incidence across Europe is approximately 5 per 100,000 children and 2 per 100,000 adults. Some have only mild symptoms, such as petechiae, purpura, nosebleeds, bleeding gums, heavy periods, and fatigue, but occasionally ITP causes serious bleeding in the brain, gastrointestinal or urinary tract, and very rarely an intracranial hemorrhage may be fatal.