EU approves Wayrilz (rilzabrutinib) as the first BTK inhibitor to treat immune thrombocytopenia – Sanofi

The European Commission has approved Wayrilz (rilzabrutinib), a novel, oral, reversible, Bruton’s tyrosine kinase (BTK) inhibitor, as a new treatment for immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments. This follows the positive opinion by the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP).

Wayrilz can help address the underlying causes of ITP through multi-immune modulation, targeting different pathways across the immune system.

“ITP is caused by complex immune system dysregulation leading to low platelet counts, bleeding and other often overlooked symptoms that can affect both physical and mental health, significantly impacting quality of life,” said Waleed Ghanima, MD, Head of Research and a Consultant Hematologist at Østfold Hospital, Norway. “The traditional approach to disease management focuses on restoring platelet counts and reducing bleeding risk, but patients may still experience other symptoms. Wayrilz offers a new approach, targeting the underlying cause of ITP through multi-immune modulation to help address the multi-faceted burden of this disease.”

“The approval of Wayrilz in the EU for the treatment of ITP underscores Sanofi’s commitment to leveraging our knowledge of the immune system to develop innovative treatments that make a meaningful impact on people living with rare and inflammatory diseases,” said Brian Foard, Executive Vice President, Head of Specialty Care at Sanofi. “Wayrilz has a differentiated mechanism of action, enabling multi-immune modulation to address the underlying pathology of ITP, allowing patients to benefit from an advanced treatment to help manage their disease.”

The EU approval of Wayrilz is based on the pivotal LUNA 3 phase III study (clinical study identifier: NCT04562766), in which Wayrilz met the primary and secondary endpoints, demonstrating a positive impact on sustained platelet counts as well as other ITP symptoms. The LUNA 3 phase III study, presented at the 66th American Society of Hematology Annual Meeting and Exposition, and also published in Blood, evaluated the efficacy and safety of Wayrilz compared to 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 Wayrilz arm and 32% of patients in the placebo arm). Patients receiving Wayrilz experienced the following compared to patients receiving placebo:

i) Statistically significant durable platelet response at week 25 (23% of patients in Wayrilz arm vs. 0% in placebo arm; p<0.0001)

ii) Faster time to first platelet response (36 days in Wayrilz arm vs. not reached in placebo arm; p<0.0001)

iii) Longer duration of platelet response (least square mean of 7 weeks in Wayrilz arm vs. 0.7 weeks in placebo arm)

Patients receiving Wayrilz reported an overall 10.6-point improvement in the overall quality of life domain 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 and impacts. The results of this analysis are descriptive and were not powered for statistical significance. The most common adverse reactions (incidence ≥10%) are diarrhea, nausea, headache, abdominal pain, and COVID-19.

About the LUNA 3 study
LUNA 3 (clinical study identifier: NCT04562766) was a randomized, multicenter, phase III study evaluating the efficacy and safety of Wayrilz vs. placebo in adult and adolescent patients with persistent or chronic ITP. Patients received either oral Wayrilz 400 mg twice a day or placebo through a 12- to 24-week double-blind treatment period, followed by a 28-week open-label treatment period, and then a four-week safety follow-up or long-term extension period. The adolescent part of the study is ongoing. The primary endpoint for the EU is the proportion of adult participants able to achieve platelet counts at or above 50,000/μL for at least eight out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy. Secondary endpoints included time to platelet response (platelet count ≥50 x 10⁹/L or between 30 x 10⁹/L and <50 x 10⁹/L and at least doubled from baseline in absence of rescue therapy), number of weeks maintaining a specific platelet response (i.e., doubled or within range), rescue therapy use, physical fatigue score, and bleeding score as assessed by change from baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) assessment at Week 25.

Citation: Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study. Authors: David J. Kuter, Waleed Ghanima, Nichola Cooper et al. Blood (2025) 145 (24): 2914–2926. https://doi.org/10.1182/blood.2024027336