LUNA 3 Trial Evaluation: Understanding BTK Inhibition in ITP Management

The global LUNA 3 phase 3 trial enrolled participants across 26 countries in a randomized, double-blind, placebo-controlled study with 2:1 randomization favoring rilzabrutinib. During the initial 12-week blinded period, 64% of individuals receiving rilzabrutinib achieved platelet response. The primary end point of durable platelet response was met in 23% of participants taking rilzabrutinib compared with 0% receiving placebo, demonstrating clinically meaningful sustained benefit for patients with chronic immune thrombocytopenia (ITP).

Secondary efficacy end points consistently favored rilzabrutinib across multiple measures important to patient outcomes. Individuals receiving rilzabrutinib maintained platelet response for 6.46 weeks longer overall, and rilzabrutinib responders sustained response for 8.8 weeks longer than placebo. Time to initial platelet response was notably rapid at 15 days for rilzabrutinib responders and 36 days median for all treated participants, whereas placebo recipients never achieved response. Rescue medication requirements—a critical indicator of treatment adequacy—were reduced by 52%, with only 33% of rilzabrutinib-treated individuals requiring rescue therapy compared with 58% receiving placebo. Median time to rescue was not reached in the treatment arm vs 56 days for placebo.

LUNA 3 distinguished itself as the first prospective ITP trial comprehensively assessing patient-reported quality-of-life metrics across 10 domains. All quality-of-life measures improved significantly for individuals receiving rilzabrutinib compared with placebo, with notable improvements in fatigue and bleeding scores observed as early as week 5. This dual achievement—improving both platelet counts and patient-reported outcomes—addresses the long-standing disconnect where platelet improvements with prior therapies failed to translate into better daily functioning. The quality-of-life benefits likely reflect rilzabrutinib’s reduction of the pro-inflammatory state underlying ITP, offering patients meaningful improvements beyond laboratory values.