Rilzabrutinib Improves Platelet Response, Quality of Life in Immune Thrombocytopenia Compared to Placebo

David J. Kuter, MD, DPhil

Credit: Harvard Medical School

Rilzabrutinib led to rapid and durable platelet responses, improved health-related quality of life, and was generally well-tolerated in adults with difficult to treat Immune Thrombocytopenia (ITP).¹

These findings, from the phase 3 LUNA 3 study, were presented at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California, by lead investigator David J. Kuter, MD, DPhil, program director of hematology at Massachusetts General Hospital and professor of medicine at Harvard Medical School in Boston.

“The drug is highly active in a highly refractory group of patients,” Kuter said in a statement.² “In addition to raising platelet counts, bleeding events decreased significantly and quality of life improved. The drug also worked really fast – within 15 days – and those who responded maintained a durable response for a long time.”

The ongoing LUNA 3 study enrolled adults and children of at least 10 years of age with primary persistent/chronic ITP and platelet counts less than 30×109/L within 2 weeks of study initiation. It completed its double-blind period during which participants were randomized 2:1 to oral rilzabrutinib 400 mg twice daily (n = 133) or placebo (n = 69) for up to 24 weeks and is ongoing in its 28-week open-label period following participants receiving rilzabrutinib. Participants in the placebo group who did not have responses were permitted to cross over to the open label part at week 12.¹

At baseline, participants had a similar overall median baseline age of 47 years (range, 18-80), median baseline platelet count of 15×10⁹/L. Around half (46%) received at least 5 prior ITP therapies and 28% in both arms had had prior splenectomy. The median duration of ITP was longer for the rilzabrutinib arm at 8.1 years (range, 0.3-52.2) compared with placebo at 6.2 years (range, 0.3-35.8).¹

Kuter and colleagues found that 31 (23%) of the rilzabrutinib arm met the primary endpoint of durable response, with platelet counts of at least 50×109/L for at least two-thirds of at least 8 of the last 12 visits of the 24-week double-blind period, without receiving rescue therapy, compared to 0% of the placebo arm (difference, 23% [95% CI, 16-30]; P <.0001). Platelet responses of at least 50×10 9/L or 30 to less than 50 x 10⁹ L and doubled from baseline were achieved by 64% of the rilzabrutinib arm and 32% of the placebo arm at week 13. Durable responses during the double-blind and open-label parts were achieved by 29% of the rilzabrutinib arm and 25% of the overall group of the 133 participants in the rilzabrutinib arm and 60 crossover participants from the placebo arm.¹

Kuter and colleagues found that rilzabrutinib significantly reduced the need for rescue therapy by 52% compared to placebo (P = .0007). Rilzabrutinib significantly improved fatigue, even among non-durable platelet responders, with a mean change) from baseline at week 13 of 7.95 (standard error [SE], 2.13) compared with -0.13 (SE, 2.86; P = .01) on ITP-Patient Assessment Questionnaire item 10. On ITP Bleeding Scale, the rilzabrutinib arm had a mean change from baseline at week 25 of –0.04 (SE, 0.02) compared with 0.05 (SE, 0.02; P = .0006) in the placebo arm.¹

“The fatigue scores got much better among those taking the drug, and that happened whether the platelet count rose or not,” Kuter said.² “This suggests there are other aspects of ITP that affect fatigue besides platelet count.” These aspects, he suggested, could include rilzabrutinib’s anti-inflammatory action.

In terms of safety during the double-blind period, most adverse events (AEs) were grade 1 or 2, including 1 placebo-related grade 3 purpura for 8 days with no treatment change. There were 2 rilzabrutinib-related AEs, including grade 4 neutropenia lasting 14 days with no infections or change to treatment and a grade 3 serious AE of peripheral embolism in the lower left leg in a participant with multiple risk-factors who then discontinued treatment. One death occurred in the rilzabrutinib arm due to unrelated pneumonia lasting 16 days. Overall, relative to other BTK inhibitors, rilzabrutinib was well-tolerated.¹

REFERENCES
1. Kuter DJ, Ghanima W, Cooper N, et al. Efficacy and Safety of Oral Bruton Tyrosine Kinase Inhibitor (BTKi) Rilzabrutinib in Adults with Previously Treated Immune Thrombocytopenia (ITP): A Phase 3, Placebo-Controlled, Parallel-Group, Multicenter Study (LUNA 3). Presented at: ASH Annual meeting; December 7-10; San Diego, California. Abstract 5.

2. Researchers Report New Opportunities to Improve Quality of Life for People with Non-Malignant Blood Disorders. Press release. ASH. December 7, 2024.