Rilzabrutinib sustained platelet responses in the phase 3 LUNA3 trial, with 23% achieving a stable response during long-term treatment for ITP.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Sanofi’s rilzabrutinib maintained stable platelet responses during the 28-week open-label period of the phase 3 LUNA3 trial in adults with persistent or chronic immune thrombocytopenia (ITP), including patients who had not initially responded during the double-blind period. The findings, published online September 17, 2026, in The Lancet Haematology, provide longer-term evidence of rilzabrutinib’s clinical activity and safety in previously treated patients with ITP.
Long-term LUNA3 data showed continued clinical activity with oral rilzabrutinib 400 mg twice daily. Among 198 patients exposed to rilzabrutinib across the double-blind and open-label periods, 46 (23%) achieved a stable platelet response, defined as having no two platelet counts below 50 × 10⁹/L at least 4 weeks apart without an intervening platelet count of at least 50 × 10⁹/L, within 24 weeks of the initial platelet response.
Dual Mechanism of Action: Targeting Pathophysiology in Chronic ITP
Rilzabrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor that modulates immune signaling involved in antibody-mediated platelet destruction. BTK inhibition affects B-cell and Fc receptor-dependent pathways that contribute to immune dysregulation in ITP.
ITP is an autoimmune disorder characterised by low platelet counts caused by immune-mediated platelet destruction and impaired platelet production. Persistent and chronic disease can become difficult to control when patients lose responses to corticosteroids, immunoglobulins or other treatments.
LUNA3 Evaluated Response Durability
LUNA3 was a multicentre, randomised phase 3 trial conducted at 103 centres across 24 countries. During the double-blind period, adults with primary persistent or chronic ITP who had previously responded to intravenous or anti-D immunoglobulins or corticosteroids were randomised 2:1 to rilzabrutinib 400 mg twice daily or placebo.
Patients entered the 28-week open-label period after completing the 24-week double-blind period or earlier if they failed to meet predefined response criteria. Of 202 patients randomised during the double-blind period, 180 entered the open-label phase. This included 115 patients originally assigned to rilzabrutinib and 65 assigned to placebo.
The stable platelet response rate was 23% overall among rilzabrutinib-exposed patients, with 31 of 133 patients (23%) in the original rilzabrutinib group and 15 of 65 (23%) in the original placebo group achieving the endpoint.
The response among patients initially assigned to placebo indicates that some patients who did not receive rilzabrutinib during the double-blind period subsequently achieved sustained platelet control after entering the open-label phase. Fourteen of 65 patients (22%) in the original placebo group achieved a durable platelet response during the open-label period.
A separate exploratory endpoint assessed complete response, defined as a platelet count of at least 100 × 10⁹/L on two consecutive visits at least 5 days apart, without bleeding or rescue ITP therapy. Complete response occurred in 42 of 180 patients (23%).
Patient-reported outcomes also remained stable or improved. Physical fatigue showed a maximum mean change from baseline of 11.7 points, while the mean change in bleeding score was −0.13.
Safety Profile Remained Manageable
Treatment-related adverse events occurred in 46 of 180 patients (26%). Diarrhoea and nausea were the most common, each occurring in 17 patients (9%), and were predominantly grade 1 or 2.
Four patients (2%) experienced treatment-related grade 3 adverse events: hypertension, petechiae, interstitial lung disease, and bronchopulmonary aspergillosis with cytomegalovirus viraemia. Two patients (1%) experienced serious treatment-related adverse events involving interstitial lung disease and bronchopulmonary aspergillosis with CMV viraemia.
No deaths occurred during the open-label period. Median follow-up was 196 days.
LUNA4 Will Test Earlier-Line Treatment
The LUNA3 long-term extension will provide additional data on the durability and safety of rilzabrutinib in difficult-to-treat ITP.
The ongoing phase 3 LUNA4 study (NCT07007962) is evaluating rilzabrutinib in adults with ITP who have failed first-line treatment. The study will assess whether earlier use of rilzabrutinib can produce sustained treatment-free responses.
The LUNA3 findings therefore provide longer-term evidence of platelet activity, including in patients who initially failed to respond during the double-blind period, while LUNA4 will determine whether the treatment can deliver clinically meaningful responses earlier in the ITP treatment pathway.
Reference
Kuter D, Ghanima W, Cooper N et al., Clinical activity and safety of rilzabrutinib in patients with previously treated immune thrombocytopenia (LUNA3): results from the open-label period of a phase 3 trial, The Lancet Haematology, 17 September 2026, https://doi.org/10.1016/S2352-3026(26)00193-6
Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP) (LUNA 3), ClinicalTrials.gov ID NCT04562766
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.