The U.S. Food and Drug Administration (FDA) has approved rilzabrutinib (Wayrilz), a Bruton’s tyrosine kinase (BTK) inhibitor, for adults with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The approval was based on the pivotal LUNA 3 phase III study (ClinicalTrials.gov identifier NCT04562766), in which rilzabrutinib met the primary and secondary endpoints, showing a positive impact on sustained platelet counts and other ITP symptoms.
“The burden of [ITP] can be both physical and emotional, with significant overlooked symptoms that can impact various aspects of daily living,” said Caroline Kruse, President and Chief Executive Officer at the Platelet Disorder Support Association. “We are pleased to have a new treatment option [in rilzabrutinib] that can help ease the ongoing strain of managing the disease for patients and their families."
As a novel oral, reversible, BTK inhibitor, rilzabrutinib can help address the root causes of ITP through multi-immune modulation, targeting different pathways across the immune system. It is the first of these kinds of drugs to be approved in the United States for the treatment of ITP.
More on LUNA 3
The LUNA 3 trial—results of which were presented by Kuter et al during the Plenary Session of the 66th American Society of Hematology Annual Meeting & Exposition (Abstract 5)—evaluated the efficacy and safety of rilzabrutinib compared with placebo in adults (n = 202) with persistent or chronic ITP. Patients who achieved platelet count response at 12 weeks were eligible to continue the full 24-week double-blind period (64% of patients in the rilzabrutinib arm and 32% of patients in the placebo arm).
Patients receiving rilzabrutinib experienced the following compared to patients receiving placebo:
- Statistically significant durable platelet response at week 25 (23% of patients in the rilzabrutinib arm vs 0% in placebo arm; P < .0001)
- Faster time to first platelet response (36 days in rilzabrutinib arm vs not reached in placebo arm; P < .0001)
- Longer duration of platelet response (least square mean of 7 weeks in rilzabrutinib arm vs 0.7 weeks in placebo arm).
Patients receiving rilzabrutinib reported an overall 10.6-point improvement across nine health-related quality-of-life measures compared to a 2.3-point increase in the placebo arm, based on The Immune Thrombocytopenia Patient Assessment Questionnaire, a clinical tool designed to measure ITP symptoms. The results of this analysis are descriptive and were not powered for statistical significance.
The most common adverse reactions (incidence ≥ 10%) reported in patients receiving rilzabrutinib were diarrhea, nausea, headache, abdominal pain, and COVID-19 infection.
“Traditionally, [ITP] management has focused on restoring platelet counts and reducing bleeding risk, which for some patients may result in suboptimal responses, persistent symptoms, or unacceptable treatment complications,” said LUNA 3 investigator David Kuter, MD, Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School. “Through multi-immune modulation, rilzabrutinib can offer a new option for patients, including those who fail steroids or do not respond to existing treatment.”
Rilzabrutinib received Fast Track and Orphan Drug Designations from the FDA for ITP. Most recently, the FDA granted the agent Orphan Drug Designation for three additional rare diseases: warm autoimmune hemolytic anemia, IgG4-related disease (IgG4-RD; Fast Track Designation also received), and sickle cell disease.
