Regulatory Pathways and Pivotal Trial Characteristics of Medicines Designated under the European Medicines Agency’s Priority Medicines Scheme Approved between 2018 and 2024

The European Medicines Agency (EMA) PRIority MEdicines (PRIME) scheme supports the development of medicines addressing unmet medical needs through early scientific and regulatory guidance. The aim of this study was to describe the regulatory pathways and pivotal trial characteristics of PRIME-designated medicines that received a positive Committee for Medicinal Products for Human Use (CHMP) opinion between 2018–2024. In this retrospective descriptive analysis, public EMA documents were reviewed. Extracted variables included regulatory characteristics (orphan drugs designation, advanced therapy medicinal products, new active substances, accelerated assessment, conditional marketing authorisation, exceptional circumstances and withdrawals), procedural timelines and pivotal trial features (phase, randomisation, blinding, comparator, number of arms, sample size and objectives). The analysis was conducted in two parts. In the first part, medicine was the unit of analysis to describe characteristics and regulatory pathways. In the second part, the unit of analysis was the medicine-indication pair defined as a unique combination of a medicine and an authorised indication and used to describe the main studies on which the CHMP based its positive opinion. Different indications for the same medicine were analysed separately when supported by distinct evidence packages, whereas indications supported by a common evidence package were analysed jointly to avoid double counting. Categorical variables were expressed as frequencies and proportions. Time intervals were calculated in calendar days and summarised as medians with interquartile range (IQR). Thirty-six PRIME-designated medicines received a positive CHMP opinion between 2018 and 2024. Oncology was the most frequent therapeutic area (12/36, 33.3%), followed by haematology-haemostaseology (8/36, 22.2%). The median time from PRIME eligibility to marketing authorisation application (MAA) submission was 844 calendar days (IQR 644–1259). Accelerated assessment (AA) was requested for 32 of the 36 medicines (88.9%). Although 27 of these requests were initially approved by the CHMP and/or the Committee for Advanced Therapies (CAT), 15 were later reverted to the standard review timeline during the assessment process. As a result, only 12 of the applications underwent AA. The median time from the start of the regulatory assessment to receipt of a positive CHMP opinion was 263.5 calendar days (IQR 201.3–325.3). Nineteen medicines received conditional marketing authorisation (CMA) (19/36, 52.8%) and two were authorised under exceptional circumstances (5.6%). Of the 36 medicines, 33 received a positive CHMP opinion for a single indication and 3 for two indications, resulting in 39 medicine-indication pairs. A total of 58 pivotal/main studies were identified from European Public Assessment Reports (EPARs) across the 39 medicines-indication pairs. The median sample size was 74.5 patients (IQR 33–161), and studies were predominantly open-label (45/58, 77.6%) and single-arm (35/58, 60.3%). By the end of 2025, among the 19 medicines initially granted a CMA, 11 medicines (57.9%) remained under CMA and 5 (26.3%) had been converted to standard marketing authorisations. Four medicines were subsequently withdrawn from the EU market. Approval of PRIME-designated medicines in the EU was frequently based on non-randomised and non-comparative evidence, with CMA. The evaluation process was expedited for a minority of the products applied. The findings reflect the challenges of evidence generation for rare and serious diseases with unmet medical needs and underscore the importance of post-authorisation evidence generation.