First Positive Phase 3 BTK Inhibitor Study in ITP Shows Significant Patient Benefit with Rilzabrutinib

Significant findings from the pivotal LUNA 3 phase 3 study highlight the efficacy and safety of rilzabrutinib, an oral BTK inhibitor, in treating adults with persistent or chronic immune thrombocytopenia (ITP). This rare autoimmune disorder is characterized by low platelet counts, leading to a heightened risk of bleeding and significant fatigue, severely impacting the quality of life.

The study showed that 65% of patients receiving rilzabrutinib achieved a platelet response, compared to only 33% of those on a placebo. The primary endpoint, durable platelet response, was significantly higher in the rilzabrutinib group (23%) versus none in the placebo group. Secondary endpoints also favored rilzabrutinib, with notable reductions in bleeding, fewer weeks requiring rescue therapy, and significant improvements in physical fatigue and overall quality of life.

Presented at the 66th American Society of Hematology (ASH) Annual Meeting in San Diego, these results underscore rilzabrutinib’s potential as the first BTK inhibitor for ITP. David Kuter, MD, the study’s author, emphasized the importance of these findings for patients who do not respond well to current treatments, highlighting the meaningful and sustained improvements across multiple aspects of the disease.

The LUNA 3 study enrolled adult patients with severe low platelet counts, administering rilzabrutinib 400 mg twice daily or a placebo over a period of up to 24 weeks, followed by an open-label period of 28 weeks. The results were compelling: patients on rilzabrutinib were three times more likely to achieve a platelet response than those on placebo, with a median time to response of just 15 days for responders.

In addition to the primary and secondary endpoints, significant improvements were observed in bleeding scores and physical fatigue. Patients on rilzabrutinib had a marked reduction in the need for rescue therapy by 52% compared to placebo. The sustained improvement in fatigue was evident through week 25, even in patients who did not achieve a durable platelet response.

The safety profile of rilzabrutinib was consistent with previous studies, with similar rates of adverse events (AEs) between the rilzabrutinib and placebo groups. The most common treatment-related AEs were mild to moderate, including diarrhea, nausea, headache, and abdominal pain.

Rilzabrutinib is currently undergoing regulatory review in both the US and the EU, with a US FDA target action date set for August 29, 2025. Dietmar Berger, MD, PhD, Chief Medical Officer and Global Head of Development at Sanofi, expressed optimism about rilzabrutinib's potential to significantly improve patient outcomes not only in ITP but also in other rare blood and autoimmune disorders, owing to its ability to target BTK.

Beyond ITP, rilzabrutinib is being investigated for various immune-mediated diseases, including warm autoimmune hemolytic anemia (wAIHA) and asthma, with promising phase 2 study results also presented at ASH. This broad research underscores the potential applicability of rilzabrutinib in treating diverse conditions involving immune system dysregulation.

The LUNA 3 study, involving a randomized, multicenter, phase 3 design, evaluated rilzabrutinib against a placebo in adult and adolescent patients. The study's primary endpoint was a durable platelet response, defined as achieving platelet counts at or above 50,000/μL for a substantial portion of the blinded treatment period without needing rescue therapy. Secondary endpoints included the number of weeks with platelet responses, time to response, use of rescue therapy, physical fatigue, and bleeding scores.

Rilzabrutinib, developed using Sanofi’s TAILORED COVALENCY® technology, is designed to selectively inhibit BTK while minimizing the risk of off-target side effects. It has received fast track designation from the US FDA for the treatment of ITP and orphan drug designation, indicating its potential to address significant unmet medical needs.

ITP, a complex autoimmune disorder, involves both increased platelet destruction and decreased production, posing severe bleeding risks and impacting patients' quality of life. Rilzabrutinib’s multiple mechanisms targeting BTK in B cells and macrophages could address these underlying disease processes, offering a new therapeutic avenue for ITP patients.

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