LUNA 3 Trial Shows Positive Results for ITP

Platelet response was achieved in 65% (n=86) of patients receiving rilzabrutinib compared to 33% (n=23) of patients on placebo. The primary endpoint was met, with rilzabrutinib demonstrating durable platelet response in 23% of ITP adult patients compared to 0% on the placebo arm (p<0.0001), as well as key secondary endpoints including reduced bleeding, number of weeks with platelet response, the need for rescue therapy use, and improved physical fatigue and quality of life measures. These results were presented today at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, December 7-10, 2024.

David Kuter, MD;; Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, study author; “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.”

In the pivotal LUNA 3 study, adult patients with persistent or chronic ITP and severely low platelet counts (median of 15,000/μL) received oral rilzabrutinib 400 mg twice a day (n=133) or placebo (n=69) for up to 24 weeks followed by 28 weeks of open-label period and demonstrated the following results:

• i. 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.
• ii.  The primary endpoint of durable platelet response, defined as the proportion of participants able to achieve 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 in the absence of rescue therapy was met in 23% (n=31) of patients receiving rilzabrutinib compared to 0% of patients on placebo (p<0.0001).
• iii. For the combined double-blind and open-label periods, durable response was achieved in 29% (n=38) of rilzabrutinib-randomized patients as of the data cutoff. Results of additional patients following data cutoff have not yet been analyzed.
• iv. Significant improvements were observed with rilzabrutinib vs. placebo 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).
• v. 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.
• vi. Rilzabrutinib significantly reduced the need for rescue therapy by 52% compared to placebo (p=0.0007).
• vi,.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). The improvement of fatigue was sustained through week 25 and was also noted in non-durable platelet responders, along with improved outcomes in other quality-of-life domains.
  
   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%).

Rilzabrutinib is an investigational medicine, and its safety and efficacy have not been fully evaluated by any regulatory authority. Rilzabrutinib is 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. Positive results from a phase II study of rilzabrutinib in warm autoimmune hemolytic anemia (wAIHA) and preclinical data in sickle cell disease were also presented at ASH.

About the LUNA 3 study; LUNA 3 (NCT04562766) is a randomized, multicenter, phase III study evaluating the efficacy and safety of rilzabrutinib vs. placebo in adult and adolescent patients with persistent or chronic ITP. Patients received either oral rilzabrutinib 400 mg twice a day or placebo through a 12- to 24-week double-blind treatment period, followed by a 28-week open-label treatment, and then a 4-week safety follow-up or long-term extension period. The adolescent part of the study is ongoing. The primary endpoint is durable platelet response, defined as the proportion of participants able to achieve 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 in the absence of rescue therapy. Secondary endpoints include the number of weeks with and time to platelet responses, rescue therapy use, physical fatigue score, and bleeding score.