Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study

Rilzabrutinib is a covalent, reversible Bruton tyrosine kinase inhibitor targeting multiple immune thrombocytopenia (ITP)-related mechanisms. The phase 3 LUNA3 study in previously treated adults with persistent/chronic ITP evaluated oral rilzabrutinib 400 mg twice daily (n = 133) vs placebo (n = 69) for 24 weeks. At baseline overall, median age was 47 years, 63% female, 7.7 year median ITP duration, and 28% prior splenectomy. Overall (N = 202), 85 (64%) rilzabrutinib and 22 (32%) placebo patients achieved platelet response (≥50 × 109/L or 30 × 109/L to <50 × 109/L and doubled from baseline) during the first 12 weeks and were eligible to continue. The primary end point, durable platelet response (platelet count ≥50 × 109/L for ≥two-thirds of ≥8 of the last 12 of 24 weeks without rescue therapy), was observed in 31 (23%) rilzabrutinib vs 0 placebo patients (P < .0001). All secondary efficacy end points were significantly superior for rilzabrutinib (P < .05). Median time to first platelet response was 15 days in rilzabrutinib responders. Rilzabrutinib significantly reduced rescue therapy use by 52% (P = .0007) and improved week 25 bleeding scores (P = .0006). Improved physical fatigue was sustained from week 13 (P = .01) through 25 (P = .0003). Treatment-related adverse events were mainly grade 1/2. One rilzabrutinib patient with multiple risk factors had serious treatment-related grade 3 peripheral embolism (lower left leg), and another died from unrelated pneumonia. Rilzabrutinib in patients who failed multiple previous ITP therapies showed rapid and durable platelet response, reduced rescue medication and bleeding, improved physical fatigue, and favorable safety. Trial registration: www.clinicaltrials.gov (#NCT04562766) and www.clinicaltrialsregister.eu (#2020-002063-60).

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Journal
Blood
Published
2025-03-16
DOI
https://doi.org/10.1182/blood.2024027336
Citations
33
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
53.64
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article

Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study

David Gómez‐Almaguer, Zsolt I. Lázár, Nichola Cooper, Ganna Kuzmina et al.
33 citations
Blood
Chronic Lymphocytic Leukemia Research
53.64
article

Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study

David Gómez‐Almaguer, Zsolt I. Lázár, Nichola Cooper, Ganna Kuzmina, Marie Luise Hütter‐Krönke, Elisa Lucchini, Ilya Kirgner, David J. Kuter, Ana Lisa Basquiera, Ahmed A. Daak, Waleed Ghanima, Matias Cordoba, Michael Fillitz, Chatree Chai‐Adisaksopha, Sylvain Audia, Ademar Dantas da Cunha Júnior, Howard A. Liebman, Lígia Cristina Monteiro Galindo, Chuen Wen Tan, Mengjie Yao, Imène Gouia, Wojciech Homenda, Yu Hu, Minakshi Taparia, Güray Saydam, Michelle Lee, Lei Zhang, Cristina Pascual, Ho‐Jin Shin, Huy Tran, Yoshitaka Miyakawa, Remco Diab
article en
33 citations

Abstract

Rilzabrutinib is a covalent, reversible Bruton tyrosine kinase inhibitor targeting multiple immune thrombocytopenia (ITP)-related mechanisms. The phase 3 LUNA3 study in previously treated adults with persistent/chronic ITP evaluated oral rilzabrutinib 400 mg twice daily (n = 133) vs placebo (n = 69) for 24 weeks. At baseline overall, median age was 47 years, 63% female, 7.7 year median ITP duration, and 28% prior splenectomy. Overall (N = 202), 85 (64%) rilzabrutinib and 22 (32%) placebo patients achieved platelet response (≥50 × 109/L or 30 × 109/L to <50 × 109/L and doubled from baseline) during the first 12 weeks and were eligible to continue. The primary end point, durable platelet response (platelet count ≥50 × 109/L for ≥two-thirds of ≥8 of the last 12 of 24 weeks without rescue therapy), was observed in 31 (23%) rilzabrutinib vs 0 placebo patients (P < .0001). All secondary efficacy end points were significantly superior for rilzabrutinib (P < .05). Median time to first platelet response was 15 days in rilzabrutinib responders. Rilzabrutinib significantly reduced rescue therapy use by 52% (P = .0007) and improved week 25 bleeding scores (P = .0006). Improved physical fatigue was sustained from week 13 (P = .01) through 25 (P = .0003). Treatment-related adverse events were mainly grade 1/2. One rilzabrutinib patient with multiple risk factors had serious treatment-related grade 3 peripheral embolism (lower left leg), and another died from unrelated pneumonia. Rilzabrutinib in patients who failed multiple previous ITP therapies showed rapid and durable platelet response, reduced rescue medication and bleeding, improved physical fatigue, and favorable safety. Trial registration: www.clinicaltrials.gov (#NCT04562766) and www.clinicaltrialsregister.eu (#2020-002063-60).

BloodVol. 145(24)
University of Southern California (US), Oslo University Hospital (NO), Kryvyi Rih National University (UA), Harvard University (US), University of Alberta (CA), Université de Bourgogne (FR), Universidade Estadual do Oeste do Paraná (BR), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Singapore General Hospital (SG), Tel Aviv Sourasky Medical Center (IL), Hammersmith Hospital (GB), Frankston Hospital (AU), Hospital General Universitario Gregorio Marañón (ES), Sanofi (France) (FR), Humboldt-Universität zu Berlin (DE), Ege University (TR), Massachusetts General Hospital (US), Uniwersytet Pomorski w Słupsku (PL), Hanusch Hospital (AT), Sanofi (Switzerland) (CH), Sanofi (United States) (US), Wuhan No.1 Hospital (CN), Pusan National University Hospital (KR), Peninsula Health (AU), Saitama Medical University Hospital (JP), Hospital la Serena (CL), Hospital Universitario Dr José Eleuterio Gonzalez (MX), Maison des Sciences sociales et des Humanités de Dijon (FR), Petz Aladár Megyei Oktató Kórház (HU), Institute of Hematology & Blood Diseases Hospital (CN), Hospital Privado (AR), Østfold Hospital Trust (NO), Azienda Sanitaria Universitaria Integrata di Trieste (IT), Imperial College London (GB), Chiang Mai University (TH), University of La Serena (CL), Charité - Universitätsmedizin Berlin (DE), Saitama Medical University (JP)
Good health and well-being
Openalex Percentile: Top 0%
Chronic Lymphocytic Leukemia Research
53.64
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