uRADAR: European Patients Referral Frame to Improve Access to New Drugs and Therapies in Ultra-Rare Anemia Disorders and Severe Hereditary Spherocytosis

• Published in: Blood 2024-11, Vol.144, p.794-794
• Main Authors: Rodríguez Sánchez, Maria A., Collado Gimbert, Anna, Reidel, Sara, Aguilar-Martinez, Patricia, Bento, Celeste, Cela, Elena, Dedeken, Laurence, Drasar, Emma, Galacteros, Frederic, Glenthoej, Andreas, Horvathova, Monika, Koralkova, Pavla, Kulozik, Andreas E., Kunz, Joachim B., Morado-Arias, Marta, Ortuno Cabrero, Ana, Pospíšilová, Dagmar, Rab, Minke A.E., Roy, Noemi, Van Beers, Eduard J., van Wijk, Richard, Wambacq, Sarah, Diot, Claire, Gutiérrez Valle, Victoria, Mosull del Campo, Raquel, Tamana, Stella, Colombatti, Raffaella, Kountouris, Petros, Gulbis, Béatrice, Bianchi, Paola, Mañú-Pereira, Maria del Mar
• Format: Article
• Language: English
• ISSN: 0006-4971
• DOI: 10.1182/blood-2024-201501

Background: Ultra-rare anemia disorders (uRADs) are commonly neglected from health planning and clinical research hampering its timely diagnosis and leading to sub-optimal clinical management and very few treatment options. The Rare Anemia Disorders European Epidemiological Platform (RADeep) together with the ERN-EuroBloodNet have joint efforts to establish the uRADAR initiative aiming to develop a referral frame for patients affected by uRADs in the European Union. The uRADAR ultimate goal is to enable access to clinical trials (CT), including drug repurposing i.e. ERN-EuroBloodNet SATISFY Phase 2 Trial (NCT05935202). Methodology: The uRADAR disease scope includes all ultra-rare hemolytic anemias (pyruvate kinase deficiency (PKD), other rare cell enzyme and membrane defects, congenital dyserytropoietic anemias I-IV (CDAs), unstable hemoglobinopathies, ultra-rare iron metabolism defects, sideroblastic anemias and metheglobinemias. Chronic and severe forms of hereditary spherocytosis (HS) and G6PD deficiency were also considered. The RADeep uRADAR module for standardized collection of uRADs data was developed in a REDcap web application. We gathered disaggregated data by age ranges (0-11, 12-15, 16-17 and ≥18 yo) on: sex, genetic diagnosis, common CT exclusion criteria, and therapeutic intervention (splenectomy and/or blood transfusion dependence (TD)). Anemia is considered as Hb 12yo. Results: Data from 5,623 patients from 82 centers (13 EU countries, Norway and United Kingdom) has been collected, 1,302 (23%) of them with an uRAD. The cohort has a balanced age and sex distribution, except for X-linked diseases. Information about severity is available for 3,465 (62%) patients, 1,015 (78%) for the uRADs. Genetic confirmation is available for 815 (14%) patients, 308 (24%) for the uRADs. Analyzing by age ranges, we noted patients were constantly diagnosed and followed during pediatric care, however about 2/3 are lost during follow-up at adult age. RBC enzyme defects: 1,600 patients (1,175 G6PD deficiency, 415 PKD and 46 Other). Even G6PD deficiency is a non-severe disease in most cases we detected 38.4% anemic patients. In PKD 48% required therapeutic intervention. 26.7% were anemic and 10.3% remained TD after splenectomy, twice as reported for other ultra-rare enzyme defects. Membranopathies: 3,468 patients (3,146 HS, 162 Hereditary elliptocytosis-HE, 122 dehydrate