Rilzabrutinib Becomes First FDA-Approved BTK Inhibitor for ITP

Yesterday, the FDA approved rilzabrutinib (Wayrilz; Sanofi) as a first-in-class treatment for immune thrombocytopenia (ITP), a rare autoimmune disorder.¹

ITP is characterized by platelet counts below 100,000/μL, driven by both increased platelet destruction and decreased production.² In addition to bruising and bleeding, which may lead to life-threatening events like intracranial hemorrhage, patients are at risk for arterial or venous thrombosis. Many also experience symptoms that contribute to a reduced quality of life, like unexplained fatigue, cognitive impairment, and anxiety or depression.

Rilzabrutinib is an oral, reversible covalent Bruton tyrosine kinase (BTK) inhibitor. BTK is expressed in B cells, macrophages, and other immune cells and plays a central role in the inflammatory pathways involved in ITP. By selectively inhibiting BTK, rilzabrutinib may reduce disease activity while minimizing the risk of off-target adverse effects.

"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," Brian Foard, executive vice president and head of specialty care at Sanofi, said in a statement.¹

The FDA's decision was based on results from the randomized, multicenter phase 3 LUNA 3 study (NCT04562766), which evaluated the efficacy and safety of rilzabrutinib vs placebo in adults and adolescents with persistent or chronic ITP.³ Participants received 400 mg of oral rilzabrutinib twice daily or placebo during a 12- to 24-week double-blind period, followed by a 28-week open-label phase and a 4-week safety follow-up or long-term extension period.²

The trial’s primary end point was durable platelet response, defined as achieving platelet counts at or above 50,000/μL for at least 8 of the last 12 weeks of the double-blind period without rescue therapy. Secondary end points included time to and duration of platelet response, use of rescue therapy, bleeding scores, and physical fatigue scores.

Although the adolescent portion of the study is ongoing, results from adult patients were presented at the 2024 American Society of Hematology Annual Meeting and Exposition. Of the patients analyzed, 133 received rilzabrutinib and 69 received a placebo. A platelet response (≥ 50,000/μL or ≥ 30,000 to < 50,000/μL and doubled from baseline) was achieved in 65% (n = 86) of the rilzabrutinib cohort compared with 33% (n = 23) in the placebo group.

At week 25, durable platelet response was achieved in 23% (n = 31) of patients receiving rilzabrutinib and 0% of those on placebo (P < .0001). Based on data from both study periods, a durable response was achieved in 29% (n = 38) of patients treated with rilzabrutinib.

Rilzabrutinib also significantly improved bleeding symptoms, with a mean (SE) change in the Immune Thrombocytopenia Purpura Bleeding Score from baseline to week 25 of –0.04 (0.02) vs 0.05 (0.02) for placebo (P = .0006). Additionally, the need for rescue therapy was reduced by 52% compared with placebo (P = .0007).

Clinically meaningful improvements in fatigue were reported as early as week 13, based on item 10 of the ITP Patient Assessment Questionnaire. The least squares (LS) mean change from baseline was 8.0 for rilzabrutinib vs –0.1 for placebo (LS mean difference, 8.1; P = .01). These improvements were sustained through week 25 and also observed in patients who did not achieve a durable platelet response. Additional benefits were seen across other quality-of-life domains.

Rilzabrutinib’s safety profile was consistent with previous studies, with adverse event rates similar in both patient groups. The majority of treatment-related adverse events were mild or moderate, with the most common being diarrhea (23%), nausea (17%), headache (8%), and abdominal pain (6%).

“I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile,” David Kuter, LUNA 3 investigator and director of clinical hematology at Massachusetts General Hospital, said in a press release.

Rilzabrutinib is also being studied across a range of other immune-mediated diseases, including warm autoimmune hemolytic anemia and sickle cell disease.

“Based on its ability to target BTK, an enzyme that plays a critical role in many types of immune cells, we believe rilzabrutinib also has the potential to improve patient outcomes in multiple rare blood and autoimmune disorders,” Dietmar Berger, MD, PhD, chief medical officer and global head of development at Sanofi, said in a press release.

References

1. Sanofi's Wayrilz approved in US as first BTK inhibitor for immune thrombocytopenia. News release. Sanofi. August 29, 2025. Accessed August 30, 2025. https://www.sanofi.com/en/media-room/press-releases/2025/2025-08-29-21-50-18-3141825
2. ASH: rilzabrutinib demonstrated significant patient benefit in the first positive phase 3 study of a BTK inhibitor in ITP. News release. Sanofi. December 7, 2024. Accessed August 30, 2025. https://www.sanofi.com/en/media-room/press-releases/2024/2024-12-07-16-30-00-2993342
3. Study to evaluate rilzabrutinib in adults and adolescents with persistent or chronic immune thrombocytopenia (ITP) (LUNA 3). ClinicalTrials.gov. Updated February 10, 2025. Accessed August 30, 2025. https://clinicaltrials.gov/study/NCT04562766