Rilzabrutinib Nets Approval in Pretreated Immune Thrombocytopenia

The FDA has approved rilzabrutinib (Wayrilz) for the treatment of adult patients with persistent or chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.1

The regulatory decision was supported by data from the pivotal phase 3 LUNA 3 trial (NCT04562766).2 Findings from LUNA 3 presented during the 2024 ASH Annual Meeting revealed that patients who received rilzabrutinib (n = 133) achieved a 25-week platelet response rate of 23% (95% CI, 16%-30%) compared with 0% (95% CI, 0%-0%) among those who received placebo (n = 69; P < .0001). Moreover, the median time to first platelet response was 36 days in the investigational arm and was not reached in the placebo arm (P < .0001). The duration of platelet response was a least square mean of 7 weeks in the rilzabrutinib arm vs 0.7 weeks in the placebo arm.1

“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 chief executive officer at the Platelet Disorder Support Association, stated in a news 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."

LUNA 3 was a multicenter study that enrolled patients who were at least 18 years of age with primary persistent or chronic immune thrombocytopenia.2 Patients were also required to have 2 platelet counts of at least 30 × 109/L at least 5 days apart during the screening period, with no single platelet count above 35 × 109/L within 14 days of treatment.

Patients were randomly assigned 2:1 to receive oral rilzabrutinib at 400 mg twice daily or placebo during the 24-week double-blind period. At the conclusion of week 12, patients were evaluated for platelet response, which was defined as at least 1 platelet count of at least 50 × 109/L or 30 × 109/L to less than 50 × 109/L and at least a doubling from baseline in the absence of rescue therapy during the first 12 weeks. Patients who achieved a platelet response could continue with double-blinded treatment through week 24 and nonresponders could discontinue study treatment or enter the 28-week open-label period to receive rilzabrutinib at 400 mg twice daily.

The primary end point was durable platelet response, which was defined as platelet counts of at least 50 × 109/L for two-thirds or more of at least 8 consecutive weekly scheduled platelet measurements during the last 12 weeks in the absence of rescue therapy. Key secondary end points included number of weeks with platelet count of at least 50 × 109/L or at least 30 × 109/L to less than 50 × 109/L and at least doubled from baseline in the absence of rescue therapy, number of weeks with platelet counts of at least 30 × 109/L and at least doubled from baseline in the absence of rescue therapy, time to first platelet count of at least 50 × 109/L or at least 30 × 109/L to at least 50 × 109/L and at least doubled from baseline, proportion of patients requiring rescue therapy, and quality of life measures.

Additional findings from LUNA 3 showed that 64% of patients achieved a platelet response in during the first 12 weeks of treatment in the investigational arm vs 32% in the control arm. The median time to platelet response among patients who responded to rilzabrutinib was 15 days. Most patients in the placebo arm (58%) required rescue therapy; patients in the rilzabrutinib arm received rescue therapy at a rate of 33%.

Patients in the rilzabrutinib arm experienced a 10.6-point improvement across 9 health-related quality of life measures per The Immune Thrombocytopenia Patient Assessment Questionnaire; patients in the control arm had a 2.3-point increase.

In terms of safety, patients in the rilzabrutinib and placebo arms experienced any-grade adverse effects (AEs; 83% vs 75%), serious AEs (9% vs 12%), and grade 3 or higher AEs (11% vs 14%). Eight patients discontinued therapy with rilzabrutinib due to AEs; no patients in the placebo arm discontinued treatment.

In April 2020, the FDA granted fast track designation to rilzabrutinib for the treatment of patients with immune thrombocytopenia.3 The BTK inhibitor also received orphan drug designation from the FDA, with similar orphan designations in Japan and the European Union.1

"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,” David Kuter, MD, DPhil, director of Clinical Hematology at Massachusetts General Hospital and a professor of medicine at Harvard Medical School, in Boston, added in the news 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.”

References

1. Sanofi’s Wayrilz approved in US as first BTK inhibitor for immune thrombocytopenia. News release. 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
2. Kuter DJ, Ghanima W, Cooper N, et al. Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study. Blood. 2025;145(24):2914-2926. doi:10.1182/blood.2024027336
3. Rilzabrutinib granted FDA fast track designation for treatment of immune thrombocytopenia. News release. Sanofi. November 18, 2020. Accessed September 2, 2025. https://www.sanofi.com/en/media-room/press-releases/2020/2020-11-18-06-15-00-2128828