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.1

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.2

Kuter sat down with HCPLive 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 HCPLive. “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.”

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. 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.

2. 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