Efficacy and Safety of Rilzabrutinib in the Treatment of Chronic Immune Thrombocytopenia: Results from the Phase 3 LUNA3 Study.

Immune Thrombocytopenic Purpura (ITP) is an acquired autoimmune hematologic disorder, with a global prevalence ranging from 10 to 23 cases per 100,000 people, and an estimated incidence of approximately 2 to 4 cases per 100,000 person-years in the general population, including both adults and children. ITP is characterized by platelet destruction mediated by autoantibodies, along with insufficient platelet production. This mechanism results in thrombocytopenia (platelet counts <100 × 10⁹/L), increasing the risk of bleeding and negatively impacting health-related quality of life (HRQoL).

The phase 3 LUNA3 clinical trial evaluated the efficacy and safety of rilzabrutinib, an oral, reversible, and covalent Bruton’s tyrosine kinase (BTK) inhibitor, in adults with persistent or chronic ITP who had been previously treated with multiple therapies. A total of 202 patients were randomized in a 2:1 ratio, with 133 assigned to the rilzabrutinib group and 69 to the placebo group. Participants received rilzabrutinib 400 mg twice daily or placebo for 24 weeks. The primary endpoint was durable platelet response, defined as platelet counts ≥50 × 10⁹/L for at least two-thirds of the last 12 weeks without the need for rescue therapy.

The results showed that 23% of patients treated with rilzabrutinib achieved a durable platelet response, compared to 0% in the placebo group (P < 0.0001). During the first 12 weeks, 64% of patients on rilzabrutinib achieved an initial platelet response, allowing continuation in the study, compared to only 32% in the control group. The median time to response was 15 days among rilzabrutinib responders. The treatment also demonstrated superiority across all secondary efficacy outcomes, including a significant 52% reduction in the need for rescue therapy (P = 0.0007) and improvement in bleeding scores as early as week 5.

Beyond hematologic parameters, rilzabrutinib provided meaningful clinical benefits related to quality of life. There was a significant improvement in physical fatigue (measured by the ITP-PAQ) at weeks 13 and 25, with a mean difference of 8 to 12 points compared to placebo. Improvements were also observed in psychological health, symptoms, social activity, and functional capacity. These findings highlight the importance of considering not only platelet count control but also the broader impact of ITP on patients’ daily lives.

Regarding safety, rilzabrutinib exhibited a favorable profile, with most adverse events being mild or moderate. The most common effects included diarrhea (23%), nausea (17%), headache (8%), and abdominal pain (6%). Serious adverse events were rare, with only one case of peripheral embolism and one death from pneumonia (considered unrelated to the treatment) reported. These data suggest that rilzabrutinib is a promising and well-tolerated therapeutic alternative for adult patients with chronic ITP refractory to multiple lines of therapy. 

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