David Kuter, MD

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 

, allowing patients to wean off concomitant corticosteroids, based on long-term extension data from the LUNA 3 trial.

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.

“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 

 in an exclusive interview. “Those concurrent therapies included things like corticosteroids and thrombopoietin receptor agonists, 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.

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.

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.

By April 1, 2025, a total of 69 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).

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 and/or thrombopoietin receptor agonists (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.

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.

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.

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.

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

Videos

Kuter discusses the efficacy and safety of rilzabrutinib in sustaining platelet responses and symptom improvement over the LUNA3 long-term extension.

Rilzabrutinib Investigations at ISTH 2025, with David Kuter, MD

At the International Society on Thrombosis and Haemostasis 2025 Congress, David Kuter, MD, director of clinical hematology at Massachusetts General Hospital, and other clinicians affiliated with Sanofi presented data on the company’s investigational treatment rilzabrutinib.

In a recent phase 3 trial, rilzabrutinib exhibited significantly and consistently increased platelet counts in patients with persistent and chronic 

primary immune thrombocytopenic purpura (ITP)

. These data resulted from a comparison of platelet count variability before and after rilzabrutinib using data from the phase 3 LUNA3 trial.

Rilzabrutinib, an investigational medication for the treatment of a variety of immune-mediated and inflammatory diseases, including ITP. The drug itself is an oral, reversible, covalent BTK inhibitor developed by Sanofi. Granted fast track designation by the US Food and Drug Administration (FDA) in November 2020, rilzabrutinib could potentially be a first- and best-in-class treatment for several diseases.

 to discuss this and several other presentations at ISTH. He described a presentation by Donald Arnold, MD, MSc, professor of medicine at McMaster University.

“The first is an interesting presentation which is not yet fully validated and is going to be presented as a poster by Donald Arnold, looking at what’s called a platelet variability index, which is a way of assessing how stable platelet counts are from day to day,” Kuter told 

. “Dr. Arnold has devised an algorithm to assess how up and down the waves are, and he’s shown that in patients who are on rilzabrutinib, we have a much more stable platelet count than would be when the patients aren’t on rilzabrutinib.”

Kuter went on to explain a presentation by Waleed Ghanima, MD, head of research and consultant hematologist as Østfold Hospital. Ghanima pushed for the incorporation of the International Working Group (IWG) response criteria in measuring durable response in patients involved in similar trials to LUNA3.

“When we did the phase 3 study, we had a thing called durable response, which is an incredibly rigorous endpoint, having to have most of your platelet counts in the last portion of the study over 50,000. That’s a very high bar to jump over,” Kuter said. Using IWG criteria, “Ghanima was actually able to show that, in patients on rilzabrutinib, the response rate, which was 23% for durable response, rose to between 50 and 60% and was well-maintained for a long period of time.”

Kuter discussed the abstract on which he was co-author, examining the data from LUNA3. He noted the surprising data collected during the placebo cohort’s crossover period to rilzabrutinib in the second portion of the study, a 28-week open-label extension.

“What was amazing is, those who had a response in the double-blind study were able to maintain or even accentuate their durable response – again, a hard criteria – and maintain a good platelet count, and those who were on placebo in the double-blind study, when they crossed over and got the active drug, had a similar response,” Kuter said. “So basically, the open-label extension study showed that responses were well-maintained for a long period of time when we did longer exposure of patients, and indeed the responses tended to drift up a bit better.”

Ultimately, Kuter expressed excitement about the progress of rilzabrutinib and its lack of significant negative side effects.

“It’s reassuring that this drug has so little adverse events when given long-term,” Kuter said. “And again, we’re doing even longer exposure, a long-term extension trial, which is ongoing, and will give us even more information as to how safe this medication is for the long term.”

Arnold D. Effect of rilzabrutinib on platelet count variability in previously treated ITP: LUNA3 phase 3 data. Poster presented at the 2025 International Society on Thrombosis and Haemostasis Congress in Washington, D.C., June 21-25, 2025.

Press Release: ASH: rilzabrutinib demonstrated significant patient benefit in the first positive phase 3 study of a BTK inhibitor in ITP. Sanofi. December 7, 2024. Accessed July 22, 2025. https://www.sanofi.com/en/media-room/press-releases/2024/2024-12-07-16-30-00-2993342

Kuter describes several studies investigating aspects of rilzabrutinib which were presented at the ISTH 2025 Congress.

David Kuter, MD

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