EUROCOVER-CLL: Reimbursement and accessibility of new treatments in relapsed/refractory chronic lymphocytic leukemia

Magdalena Monica^1*Sabina Mujkic²Ioanna Bianchi-Manaila³Natasa Duborija-Kovacevic⁴Pero Draganic^5,6Kristina Garuolienė⁷Ariel Hammerman⁸Fanni Ispán⁹Boryana Ivanova¹⁰Agnes Männik¹¹Gergo Meresz¹²Lusine Nazaryan¹³Oleksandra Oleshchuk¹⁴Alexandra Savova¹⁵Jana Skoupa¹⁶Nikola Stefanovic¹⁷Tomas Tesar¹⁸Paweł Kawalec¹⁹

• ¹Doctoral School of Medical and Health Sciences, Jagiellonian University Medical College, Cracow, Poland
• ²Agency for Medicines and Medical Devices of Bosnia and Herzegovina, Sarajevo, Bosnia and Herzegovina
• ³Romanian Association of International Medicine Manufacturers, Bucharest, Romania
• ⁴Department of Pharmacology and Clinical Pharmacology, Medical Faculty of the University of Montenegro, University of Montenegro, Podgorica, Montenegro
• ⁵Agency for Medicinal Products and Medical Devices (HALMED), Zagreb, Croatia
• ⁶Faculty of Biotechnology and Drug Development, University of Rijeka, Rijeka, Croatia
• ⁷Pharmacy and Pharmacology Center, Faculty of Medicine, Vilnius University, Vilnius, Lithuania
• ⁸Medison Pharma, Petah-Tiqva, Israel
• ⁹Department of Reimbursement, National Health Insurance Fund Management, Budapest, Hungary
• ¹⁰Department of Organization and Economics of Pharmacy, Faculty of Pharmacy,, Medical University of Sofia, Sofia, Bulgaria
• ¹¹Institute of Family Medicine and Public Health, University of Tartu, Tartu, Estonia
• ¹²Hungarian Health Economics Association, Budapest, Hungary
• ¹³Yerevan State Medical University, Yerevan, Armenia
• ¹⁴Department of Pharmacology with Clinical Pharmacology, Horbachevsky Ternopil National Medical University, Ternopil, Ukraine
• ¹⁵Department of Organization and Economics of Pharmacy, Medical University of Sofia, Sofia, Bulgaria
• ¹⁶EconHealth s.r.o., Prague, Czechia
• ¹⁷Department of Pharmacy, Faculty of Medicine, University of Nis, Nis, Serbia
• ¹⁸Department of Organization and Management of Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
• ¹⁹Department of Nutrition and Drug Research, Faculty of Health Sciences, Jagiellonian University Medical College, Cracow, Poland

Background: Despite recent therapeutic advances in chronic lymphocytic leukemia (CLL), access to innovative treatments may still be uneven outside Western Europe. This study aimed to explore reimbursement policy and access to novel targeted CLL therapies across selected countries and to analyze factors associated with differences in treatment availability and reimbursement timelines.Methods: Reimbursement frameworks, timelines, and accessibility of six novel CLL therapies were assessed across 15 countries in Central and Eastern Europe, the Balkans, Armenia, and Israel. Data were collected via expert surveys in late 2024, based on publicly available national and regional sources. The survey covered reimbursement extent, timelines, policy restrictions, coverage pathways, and health technology assessment (HTA) evaluations. Comparative analyses examined regional differences in reimbursement and their potential drivers. Spearman's rank correlation was used to explore associations between the number of reimbursed therapies, reimbursement delays, and demographic, macroeconomic, and epidemiological variables.The number of reimbursed therapies ranged from zero (Ukraine, Armenia) to five (Czech Republic), with a regional mean of 2.7 (SD = 1.38) and overall mean time to reimbursement of 29.3 months (SD = 21.4). Ibrutinib, reimbursed in 13 countries, had the longest mean reimbursement delay (35.6 months), while venetoclax (11 countries, 26.5 months), acalabrutinib (9 countries, 16.4 months), and zanubrutinib (6 countries, 15.2 months) had shorter delays. Gross domestic product (GPD) per capita showed a moderate positive correlation with the number of reimbursed therapies (ρ = 0.673, p = 0.006). Borderline significant associations were noted for CLL incidence and mortality (p = 0.050). Reimbursement indications were often restricted, particularly for patients without deletion 17p or TP53 mutations who experienced late relapses. Data on HTA outcomes and the number of treated patients were limited in several countries, and common challenges included funding constraints, administrative barriers, and the lack of centralized rare disease policies.Conclusions: Significant disparities in access to targeted CLL therapies persist across the analyzed countries, with the number of reimbursed therapies positively correlated with GDP per capita.