Rilzabrutinib Preserves Platelet Response in ITP Through Extension Study, With David Kuter, MD

Rilzabrutinib has continued to demonstrate sustained platelet responses and symptom improvement in patients with immune thrombocytopenia (ITP), allowing patients to wean off concomitant corticosteroids, based on long-term extension data from the LUNA 3 trial.1

Presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition by David Kuter, MD, director of clinical hematology at Massachusetts General Hospital and professor of medicine at Harvard Medical School, these data reinforce the positive results from the base LUNA 3 trial, which saw rilzabrutinib improve physical fatigue and bleeding scores while maintaining a favorable safety profile.1

“To be honest, I think that the major outcome of the long-term extension study is that patients were able to wean off or down on their concurrent ITP therapies,” Kuter told HCPLive in an exclusive interview. “Those concurrent therapies included things like corticosteroids and thrombopoietin receptors, and more than half of the patients declined or ceased those medications.”

LUNA 3 was a randomized, double-blind study conducted across 155 sites worldwide. Patients were eligible for enrollment if they had primary ITP with a duration of >6 months in patients aged 12 to <18 years and a duration of >3 months in patients aged ≥18 years. Additionally, patients were required to have an average of 2 platelet counts ≥5 days apart of <30,000/µL during the screening period and no single count >35,000/µL within 14 days prior to the first dose, as well as hemoglobin >9 g/dL within 1 week prior to study day 1.2

Patients would be randomly assigned to receive either rilzabrutinib 400 mg or a matching placebo dose twice daily for 24 weeks. The primary outcome was durable platelet response during the last 6 weeks of the 24-week blinded treatment period. Secondary outcomes included the number of weeks with platelet count ≥50,000/µL or between ≥30,000/µL and <50,000/µL, the proportion of patients requiring rescue therapy, and the proportion of patients who achieved stable platelet response within a period of 24 weeks following initial achievement, among other endpoints.2

After completing LUNA3, patients who had response (defined as platelet count ≥50x10^9/L or ≥30x10^9/L and at least doubled from baseline at ≥50% of visits without rescue therapy) during the last 8 weeks of the base trial. During the extension, patients would be given oral rilzabrutinib 400mg until loss of response on 2 consecutive visits or for safety reasons.1

By April 1, 2025, a total of 169 patients had enrolled in the extension. Median age was 52 years (range, 18-80), and 72% were female. The median duration of ITP was 9.6 years (range, 0.3-42.7), and the median number of unique prior therapies was 4 (range, 1-9; 26% splenectomized). Additionally, 97% of patients had received corticosteroids. Median baseline platelet count was 18x10^9/L (range, 2-54x10^9/L).1

At follow-up visits, median platelet counts ranged from 83-168x10^9/L through 33 months of the extension. During the first 12 months, patients had platelet counts ≥50x10^9/L or between 30-50x10^9/L, and at least doubled from baseline for an average of 88% visits (standard deviation [SD], 24%). Of patients who had received rilzabrutinib monotherapy (n = 22) or rilzabrutinib and concomitant corticosteroids (n = 47), median platelet counts at entry were 78x10^9/L (range, 20-371x10^9/L) and 115x10^9/L (range, 28-877x10^9/L), respectively, and ranged from 78-270x10^9/L and 90-160x10^9/L, respectively, through month 33.1

Among the 34 patients in the extension who entered on concomitant corticosteroids, 10 discontinued, 2 reduced their dose ≥50% from the base study’s baseline, and 6 reduced their dose to <5 mg. Median platelet counts before and after corticosteroid discontinuation at last available visit were 148x10^9/L (range, 19-722x10^9/L) and 178x10^9/L (range, 3-405x10^9/L), respectively.1

In addition to these results, Sanofi has also published data from the LUMINA series of trials investigating rilzabrutinib in warm autoimmune hemolytic anemia. The company plans to investigate this medication across a broader series of autoimmune conditions in the future.

“There are other autoimmune diseases for which ITP is a paradigm for therapy,” Kuter said. “I think that studying rilzabrutinib across the border in many autoimmune diseases is going to be a very important target as we move forward.”

Editors’ Note: David Kuter, MD, MSc, reports disclosures with Amgen, Bristol Myers Squibb, Daiichi Sankyo, Merck Sharp & Dohme, Medscape, Novartis, Pfizer, Principia, Regeneron, Sanofi, and others.

References

1. Kuter D, Zhang L, Ghanima W, et al. Reduction in corticosteroid use with rilzabrutinib and sustained response in adults with persistent/chronic immune thrombocytopenia in the long-term extension period of the Phase 3 LUNA3 study. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Sanofi. Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP) (LUNA 3). ClinicalTrials.gov Identifier: NCT04562766. Updated February 10, 2025. Accessed December 12, 2025. https://www.clinicaltrials.gov/study/NCT04562766