Agency report reveals solid results from the first five years of its PRIME scheme, but also calls for improvements in focus.
The European Medicines Agency (EMA) says that its PRIME scheme for priority medicines has effectively cut the time to approval for the products that qualified to use the scheme, but it is already planning how to update the program to target the assistance more precisely.
In a report on the first five years of experience with its dedicated early and enhanced scientific and regulatory support,1 EMA says it has enabled "earlier availability of life-changing medicines." The support proved particularly valuable in reducing the time required by the applicant to answer questions from EMA during the evaluation, with smaller firms especially benefiting.
By this month, 98 medicines have qualified for the scheme, including CAR-T cell therapies, curative gene therapies, treatments for rare cancers, and a vaccine to protect against the Ebola virus. Between the start-up in March 2016 and June 2021, 18 medicines that had PRIME support obtained EU approval, 10 of them with a conditional marketing authorization. Of the approved products, seven are advanced therapies, and had on average shorter active assessment time and clock-stop duration than the average assessment time for all types of new active substances in 2020. Sixteen treatments concern rare diseases. PRIME products were more likely to be granted accelerated assessment and maintain the designation during evaluation, compared with equivalent non-PRIME submissions. In addition, a correlation was observed between compliance with scientific advice, maintenance of accelerated assessment, and a positive marketing authorization procedure outcome, confirming the findings of previous studies.
Vaccines and hematology products were particularly successful in qualifying and in winning approval. EMA speculates that the key factors may have been strong mechanism of action; high response rates in initial clinical tests, in some cases supporting a potential curative effect; and the feasibility of identifying a clinical laboratory test to support early stage proof of concept. Advanced therapies also did well, "because the submitted requests generally combined a high potential to address an unmet medical need with a usually very specific mechanism of action and strong demonstration of proof of concept." But not all products are successful, and not all applicants to the scheme qualify—far from it. In the period from March 2016 to June 30, 2021, a total of 384 requests for PRIME eligibility were received (nearly a third for oncology products), of which 372 were validated and 95 were granted, which amounts to an overall acceptance rate of around 25%.
Smaller companies accounted for nearly two thirds of the applications, with less than 1% coming from academia, but the success rate was highest among larger firms. One of the presumed reasons for rejected applications was insufficient data to support the medicine’s effect, in terms of plausibility, robustness, and magnitude. But the amount and relevance of data presented, as well as submissions either too early or too late, are also reported as factors.
The enhanced interaction with EU regulators through PRIME is seen as particularly useful for developers of more complex products and for applications that rely on smaller datasets—notably advanced therapies and treatments for orphan diseases. The scheme is assisting its first academia-led development, an advanced therapy for relapsed or refractory acute adult lymphoblastic leukaemia. The EMA report contains strong encouragement to all academic developers to interact with regulatory authorities to obtain early support for the development and clinical translation of their products.
The report's recommendations for improvements to the scheme focus on timing for entering the PRIME scheme, bringing more flexibility to scientific advice procedures for qualified products, and leveraging the knowledge built during development to build more robust marketing authorization applications that can be assessed in an accelerated manner. A toolbox with guidance on quality data is currently being finalized, and support for early contact for applicants is likely to be strengthened with a better-resourced EMA cross-functional team.