Rilzabrutinib Becomes First Approved BTK Inhibitor for Immune Thrombocytopenia

Rilzabrutinib (Wayrilz; Sanofi) received FDA approval for treatment of adults with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. The approval, based on data from the phase 3 LUNA 3 study (NCT04562766), marks the agent as the first of its kind approved for this indication.¹

3D visualization of platelets | Image Credit: © ChrisKuz - stock.adobe.com

ITP is a type of blood disorder characterized by low platelet counts, which leads to poor blood clotting—a critical aspect of wound healing. The condition can be acute, often lasting less than 12 months, or chronic. Chronic ITP typically affects adults, and particularly women, at a rate 2 to 3 times higher than men. Treatment for ITP typically focuses on reducing bleeding risk and restoring platelet counts. However, these approaches often yield suboptimal outcomes as patients experience persistent symptoms or complications.²

Rilzabrutinib is an oral, reversible Bruton tyrosine kinase (BTK) inhibitor with multi-immune modulation capabilities. This is novel in the treatment landscape of ITP as treatment has previously focused on symptom relief or control, rather than addressing the root cause of the condition. Rilzabrutinib selectively inhibits BTK, which is expressed in B cells, macrophages, and other immune cells, and plays a key role in the inflammatory pathways driving ITP.^3,4

“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,” study author David Kuter, MD, Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, said in a press release. “Through multi-immune modulation, [rilzabrutinib] can offer a new option for patients, including those who fail steroids or do not respond to existing treatment.”⁴

The FDA approval of rilzabrutinib is based on data from the phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group LUNA 3 study, which evaluated the safety and efficacy of rilzabrutinib vs placebo in patients with persistent or chronic ITP (n = 202). Patients received either 400 mg of rilzabrutinib or placebo orally during the 12- to 24-week double-blind treatment period, followed by a 28-week open-label treatment period, and then a 4-week safety follow-up or long-term extension period.^1,4

The primary end point is durable platelet response with secondary end points including time to platelet response (platelet count ≥50 x 109/L or between 30x109/L and <50x109/L and at least doubled from baseline in absence of rescue therapy), number of weeks maintaining a specific platelet response (ie, doubled or within range), rescue therapy use, physical fatigue score, and bleeding score.⁴

At week 25, 23% of patients treated with rilzabrutinib achieved statistically significant durable platelet responses compared with those in the placebo group (0%; P < .0001). Rilzabrutinib therapy was also associated with faster time to first platelet response (36 vs not reached; P <.0001) and longer duration of platelet response (least square mean of 7 weeks vs 0.7 weeks).⁴

Patients in the trial treated with rilzabrutinib reported a notable 10.6-point improvement across the 9 health-related quality of life measures based on The Immune Thrombocytopenia Patient Assessment Questionnaire.⁴

The safety profile was favorable, with the most common adverse effects (incidence ≥10%) being diarrhea, nausea, headache, abdominal pain, and COVID-19.⁴

“The burden of immune thrombocytopenia can be both physical and emotional, with significant overlooked symptoms that can impact various aspects of daily living,” Caroline Kruse, president and CEO at the Platelet Disorder Support Association, said in a press release. “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."⁴

REFERENCES

1. Study to evaluate rilzabrutinib in adults and adolescents with persistent or chronic immune thrombocytopenia (ITP) (LUNA 3). Updated February 10, 2025. Accessed September 2, 2025. https://clinicaltrials.gov/study/NCT04562766?term=NCT04562766&rank=1

2. Immune Thrombocytopenia (ITP). National Heart, Lung, and Blood Institute. July 24, 2025. Accessed September 2, 2025. https://www.nhlbi.nih.gov/health/immune-thrombocytopenia

3. McCormick B. Rilzabrutinib becomes first FDA-approved BTK inhibitor for ITP. AJMC. August 30, 2025. Accessed September 2, 2025. https://www.ajmc.com/view/rilzabrutinib-becomes-first-fda-approved-btk-inhibitor-for-itp

4. Sanofi’s Wayrilz approved in US as first BTK inhibitor for immune thrombocytopenia. Sanofi. August 29, 2025. Accessed September 2, 2025. https://www.news.sanofi.us/2025-08-29-Sanofis-Wayrilz-approved-in-US-as-first-BTK-inhibitor-for-immune-thrombocytopenia