Europe Enhances Regulatory Support for Tackling Unmet Medical Need

The European ambition to scheme to promote development of medicines in areas of unmet medical need—one of the central principles of the major legislative reform promised for the near future—is already getting a boost with an update of the PRIME scheme to support earlier availability of life-changing medicines.

The Priority Medicines scheme, to give it its full title, has already seen 26 medicines win a positive recommendation for approval in the European Union after benefiting from its support over the last five years. This voluntary scheme is based on close interaction and early dialogue with developers of promising medicines, and developers of a medicine that benefits can expect to be eligible for accelerated assessment when an application for a marketing authorization is made.

The European Medicines Agency, which operates the scheme, announced at the start of April that it is to put in place a more agile setting so as to be able to address queries from PRIME applicants in a shorter timeframe. The update will allow expedited scientific advice to be provided in case of issues that arise with a specific development program. In addition, a more systematic approach is to be adopted to scientific and regulatory support for each PRIME development, with the establishment of an individualized and customized roadmap and a product development tracker. These tools are intended to assist continuous dialogue between regulators and developers through detailed monitoring throughout the development process.

A further innovation is that towards the end of the development process for each product, about a year before a marketing authorization application is submitted, a specific meeting—a "submission readiness meeting"—will be scheduled to discuss the status of the development. This will include a check on implementation of previous regulatory advice, and the scope and quality of the resulting data package intended to support the marketing application. Where applicable, developers would also be expected to present mature plans for post-marketing evidence generation.

New guidance published by EMA sets out the approaches to be followed by developers and by regulators. It covers in detail the objectives, expectations, and prerequisites for the PRIME kick-off meeting and the submission readiness meeting, along with details of preparation and organizational aspects. Developers should present a briefing document at the kick-off that summarizes the product, the development program including detailed planning and timelines, information on any previous scientific advice and its implementation, and the plan, timelines and scope for scientific advice/protocol assistance requests, pediatric investigational plan, orphan drug designation, advanced therapy classification.

The developer's briefing document is also to move beyond development to issues related to market access. So it should contain the planned regulatory submission strategy, and an outline of any specific difficult or complex issues related to the product development (quality, non-clinical and clinical) and points on which support and input from the regulators and experts might be sought. It should also report interactions with health technology assessment bodies. In a sign of the times—in which EMA now openly acknowledges the unavoidable overlap between purely regulatory evaluation and the value assessment of a product—it says: "The applicant is strongly encouraged to consider and discuss requests for parallel EMA/HTA consultation as part of the series of scientific advice envisaged."

The new features result from a review of the first five years’ experience with the scheme, and will be trialed in a 12-month pilot running until March 2024. EMA's own analysis of PRIME concluded that it had had a positive impact on the authorization of new medicines that benefit patients with no current treatment options, or that offer a major therapeutic advantage over existing treatments. But increasing the flexibility of scientific advice provision was identified by the review as a key need. So too was helping applicants better prepare for the marketing authorization assessment phase.

Meanwhile, the wait goes on for the European Commission proposals on the impending major review of EU pharmaceutical legislation. These plans, under live discussion for more than three years (and under consideration for more than 20, ever since they were agreed), were initially due to appear at the end of 2022. The Commission missed that deadline, and set a new one for mid-March. It missed that too, and set another for the end of March. But at the last moment publication was again deferred, and the most recent date now is April 26. But firmly lodged in all the pre-publication talk from the Commission, the concept of unmet need is front and center. The EU official closest to the proposals, health commissioner Stella Kyriakides, promised again in March that "we will make sure we give strong incentives for innovation, especially for unmet medical needs." Medicine developers across Europe—and beyond—are impatient to see how far her proposals and the resulting legislation meet the promise.