ABSTRACT:
In the last decade, regulatory agencies have progressively employed accelerated pathways to approve medicines in cases of unmet medical needs. The study aims to determine their regulatory and incorporation status in Brazil and selected countries and the expenditures of Brazil’s Ministry of Health (MoH) from 2019 to 2023. The study analyzes medicines mentioned in the MoH’s Management Reports for the years 2021 to 2023, responsible for major acquisitions to meet legal demands. Expenditure data were extracted from the Integrated General Services Administration System for the period from 2019 to 2023, and values were adjusted. Data on health regulation and incorporation were extracted, April to June 2025, from the websites of the North American, European, and Brazilian regulatory agencies and health technology assessment (HTA) bodies of Brazil, Canada, England, the Netherlands, and Portugal. Thirteen drugs for rare diseases were analyzed. Ataluren is not registered by the FDA, having its registration renewal denied by the EMA, leading to expiry of the submission on 03/25/2025. Eteplirsen is neither registered by the EMA nor by ANVISA, volanesorsen is not registered by the FDA, and the mercaptamine salts are not registered by ANVISA. The FDA designates all these drugs as orphans, and the EMA most of them, save for three medicines. All medicines were approved through accelerated pathways in at least one agency. Only ivacaftor, Kaftrio®, and Zolgensma® were incorporated by all HTA bodies. The MoH’s total expenditure on these drugs was R$2.28 billion, with 41% of this amount spent on ataluren. Vosoritide, responsible for 10% of the amount spent, was not evaluated by any of the HTA bodies. Orphan drugs account for the largest expenditures of the MoH on litigated medicines, which may or may not be registered or incorporated. Many were approved through accelerated pathways, which may compromise the robustness of scientific evidence.