Sanofi's rilzabrutinib, an oral Bruton's tyrosine kinase (BTK) inhibitor, has shown positive results in the Phase 3 LUNA 3 trial for adults with persistent or chronic immune thrombocytopenia (ITP). The study, presented at the 66th American Society of Hematology (ASH) Annual Meeting, demonstrated the efficacy and safety of rilzabrutinib, reinforcing its potential as a first-in-class treatment for ITP. The trial met its primary endpoint, with 23% of adult ITP patients achieving a durable platelet response compared to 0% in the placebo arm (p<0.0001).
In the LUNA 3 study, adult patients with persistent or chronic ITP and severely low platelet counts (median of 15,000/μL) received either oral rilzabrutinib 400 mg twice a day (n=133) or placebo (n=69) for up to 24 weeks, followed by a 28-week open-label period. The primary endpoint was durable platelet response, defined as achieving platelet counts at or above 50,000/μL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period without rescue therapy.
Significant Outcomes
Platelet response (defined as ≥50,000/μL or ≥30,000–<50,000/μL and doubled from baseline) was achieved in 65% (n=86) of patients receiving rilzabrutinib compared to 33% (n=23) of patients on placebo. Patients on rilzabrutinib were approximately three times more likely to achieve a platelet response than patients on placebo (hazard ratio=3.1 [95% confidence interval, 1.9-4.9]; p<0.0001) and had a median time to first platelet response of 36 days vs. median not achieved by patients on placebo. Among responders on rilzabrutinib, median time to response was 15 days.
The study also met key secondary endpoints, including significant improvements in bleeding (based on the Immune Thrombocytopenic Purpura Bleeding Score), with a mean change (SE) from baseline at week 25 of –0.04 (0.02) vs 0.05 (0.02; p=0.0006). Rilzabrutinib significantly reduced the need for rescue therapy by 52% compared to placebo (p=0.0007). Significant and clinically meaningful improvements in physical fatigue (based on the Immune Thrombocytopenic Purpura Patient Assessment Questionnaire ITP-PAQ Item 10 score) were observed in patients on rilzabrutinib from baseline at week 13 with a least squares (LS) mean change of 8.0 vs. –0.1 for placebo (LS mean difference 8.1, p=0.01).
Safety Profile
The safety profile of rilzabrutinib was consistent with previous studies. The rates of adverse events (AEs) were similar in patients receiving rilzabrutinib and patients receiving placebo; the most common treatment-related AEs for rilzabrutinib were mild/moderate (grade 1/2), including diarrhea (23%), nausea (17%), headache (8%) and abdominal pain (6%).
Expert Commentary
David Kuter, MD, Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, and study author, stated, “People living with immune thrombocytopenia who cannot tolerate or do not respond to medications aimed at raising platelet counts are at risk of uncontrolled bleeding and often endure side effects from steroids and other available therapies. A significant percentage of these patients also suffer from severe fatigue and an impaired quality of life. I’m encouraged by the robust therapeutic effects I’ve seen in patients of the LUNA 3 study across all aspects of the disease, including clinically meaningful and sustained improvements in platelet count, quality of life metrics, reduction in bleeding, and a favorable safety profile.”
Regulatory Status and Future Research
Rilzabrutinib is an investigational medicine currently under regulatory review in the US and the EU, with a US Food and Drug Administration target action date of August 29, 2025. In addition to ITP, rilzabrutinib is being studied across a variety of immune-mediated diseases, including warm autoimmune hemolytic anemia (wAIHA) and asthma.
