The US Food and Drug Administration has approved Sanofi's Wayrilz (rilzabrutinib) as the first Bruton's tyrosine kinase (BTK) inhibitor for treating adults with persistent or chronic immune thrombocytopenia (ITP) who have had insufficient response to previous treatments. The approval marks a significant advancement in addressing the complex immune dysregulation underlying this rare blood disorder that affects more than 25,000 US adults.
Novel Mechanism Targets Disease Root Causes
Wayrilz represents a breakthrough approach to ITP treatment through its multi-immune modulation mechanism. As an oral, reversible BTK inhibitor, the drug targets different pathways across the immune system to address the root causes of ITP rather than merely managing symptoms. BTK is expressed in B cells, macrophages, and other innate immune cells, playing a critical role in multiple immune-mediated disease processes and inflammatory pathways.
"With its differentiated mechanism of action, Wayrilz has the potential to become a treatment of choice for immune thrombocytopenia patients who have not responded to a prior therapy," said Brian Foard, Executive Vice President, Head of Specialty Care at Sanofi. "Its multi-immune modulation approach shows promise in addressing the key drivers of immune thrombocytopenia."
LUNA 3 Study Demonstrates Superior Efficacy
The approval was based on the pivotal LUNA 3 phase 3 study, which evaluated 202 adults with persistent or chronic ITP in a randomized, multicenter trial. Patients received either oral Wayrilz 400 mg twice daily or placebo through a 12- to 24-week double-blind treatment period. The study demonstrated statistically significant improvements across multiple endpoints:
Primary Endpoint Results:
- 23% of Wayrilz patients achieved durable platelet response at week 25 compared to 0% in the placebo group (p<0.0001)
- Durable platelet response was defined as platelet counts ≥50,000/μL for more than two-thirds of at least 8 weekly measurements during the last 12 weeks
Secondary Endpoint Outcomes:
- Faster time to first platelet response: 36 days with Wayrilz versus not reached with placebo (p<0.0001)
- Longer duration of platelet response: 7 weeks (least square mean) with Wayrilz versus 0.7 weeks with placebo
- 64% of Wayrilz patients achieved platelet count response at 12 weeks compared to 32% receiving placebo
Quality of Life Improvements
Beyond platelet count improvements, patients receiving Wayrilz reported meaningful enhancements in daily functioning. Using The Immune Thrombocytopenia Patient Assessment Questionnaire, patients showed 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.
"The burden of immune thrombocytopenia can be both physical and emotional with significant overlooked symptoms that can impact various aspects of daily living," said Caroline Kruse, President and CEO at the Platelet Disorder Support Association. "We are pleased to have a new treatment option that can help ease the ongoing strain of managing the disease for patients and their families."
Safety Profile and Adverse Events
The most common adverse reactions observed in clinical trials (incidence ≥10%) included diarrhea, nausea, headache, abdominal pain, and COVID-19. The safety profile supports the drug's potential as a treatment option for patients who have not responded adequately to existing therapies.
Addressing Unmet Medical Needs
ITP is a disease of complex immune dysregulation causing low platelet counts (<100,000/μL), resulting in bleeding symptoms and thromboembolism risk. Beyond bruising and bleeding, which can include potentially life-threatening episodes like intracranial hemorrhage, patients may experience reduced quality of life, including physical fatigue and cognitive impairment.
"Traditionally, immune thrombocytopenia 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 David Kuter, MD, Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School. "Through multi-immune modulation, Wayrilz can offer a new option for patients, including those who fail steroids or do not respond to existing treatment."
Regulatory Recognition and Global Expansion
Wayrilz received Fast Track and Orphan Drug Designations from the FDA for ITP, with similar orphan designations in Japan and the EU. The FDA recently granted additional Orphan Drug Designations for three other rare diseases: warm autoimmune hemolytic anemia, IgG4-related disease, and sickle cell disease.
The drug was previously approved in the United Arab Emirates in June 2025 and is currently under regulatory review in the European Union and China. Sanofi has established the HemAssist patient support program to help patients navigate access, insurance coverage, and financial assistance options.
