The PRIME Scheme
In a previous post, the Adaptive Pathways Pilot was discussed, which is the EMA’s attempt to improve timely access for patients to new medicines by encouraging early dialogue between patients and other stakeholders. Congruent with these efforts, the EMA is developing a scheme to stimulate innovation, optimise development and accelerate assessment of medicines of major public health interest, referred to as priority medicines (PRIME). The PRIME scheme is due for launch in the first quarter of 20161.
Presently, applicants are granted accelerated assessment status just prior to the filing of an initial marketing application (MAA). However, with the introduction of the PRIME scheme sponsors will now be permitted to apply for, and be granted, accelerated assessment status much earlier. The PRIME scheme also offers the additional benefits of greater scientific and regulatory support at earlier stages of development1.
What’s on offer?
The PRIME scheme will offer support through a scientific advice procedure, which will vary depending on the product, its stage of development and, perhaps controversially, the applicant. Successful applicants will benefit from an early CHMP rapporteur appointment and a kick of meeting with the SAWP experts. Moreover, there will be opportunities to discuss development plans and possible regulatory pathways with the rapporteur and relevant committees1. The scheme will not replace the existing scientific advice or protocol assistance procedures, rather, it will be an opportunity for prospective and augmented interactions with the regulators. Drug development progress will be regularly monitored, chiefly by highlighting key milestones in the development process and advising the applicant to request scientific advice at these points (with fee reductions for SMEs), and also by asking for updates if no scientific advice is requested1.
The scheme also offers a considerable early entry advantage to SMEs and applicants from academia with products being eligible at the earlier stage of proof of principle (prior to phase II/exploratory clinical studies) as shown in the figure2 below, rather than the proof of concept stage, as is required for applicants from larger companies. In addition to the enhanced regulatory support at this stage, the EMA expects SMEs to be able to use the PRIME designation to attract investment and improve their chances of progressing to the later stages of development.
Big pharma is questioning the fairness of these proposals by arguing that medicines of a major public health interest should be eligible for entry into PRIME scheme at the proof of principle stage, regardless of the size of the company. Geert Preuveneers, executive director of regulatory affairs Europe at MSD has said “unmet medical need is not linked to whether the applicant is an SME or not”3.
However, the EMA is defiant in its support for these smaller actors who often find it difficult to progress to the proof of concept stage as a result of limited capital and development expertise. Jordi Llinares Garcia, the EMA head of product development support, when speaking at the annual EMA Review of the Year for 2016 insisted that the goal of the scheme "is to try to help those most in need and in this case SMEs are most in need at an early phase, either because they lack regulatory experience or they find it hard to raise capital to fund the later stages of development. When this happens, ideas are lost and that's something we want to avoid"3.
In order to qualify for the PRIME scheme, the applicant must submit a relatively short but detailed justification explaining (a) how the product meets an unmet clinical need and (b) the extent to which the product is expected to address the clinical need. The unmet clinical need should be justified with reference to epidemiological literature and by describing the current treatment options for a given indication. The potential of the medicine to address the unmet clinical need should be based on the clinical response and safety data generated in exploratory clinical studies. As discussed, SMEs and applicants from the academic sector may also be eligible at the proof of principle stage if they provide extremely compelling evidence of a significant observed effect in non-clinical studies combined with robust safety data from early clinical trials1.
It remains to be seen if PRIME scheme can successfully facilitate and expedite the approval of medicines which meet an unmet clinical need, but a glance across the Atlantic should be cause for optimism. The FDA’s Breakthrough Therapy Designation (BTD) was also introduced with the aim of accelerating the development of new medicines which address an unmet clinical need, and for the BTD products that have been approved so far the average time of development was around five years4 compared to previous studies that have shown development times to be around six to seven years5,6.
Overall, the scheme is intended to encourage discussion between sponsors and regulators at an earlier stage to advise applicants on their development plans and, ultimately, improve the chances of bringing medicinal products of a major public health interest to market earlier. Clearly, prospective scientific advice and the capital-raising benefits of a PRIME designation will be a huge help to smaller companies attempting to navigate the “valley of death”. However, it is not clear why these benefits would be attenuated upon the inclusion of big pharma.
- European Medicines Agency. Reflection paper on a proposal to enhance early dialogue to facilitate accelerated assessment of priority medicines (PRIME). http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2015/10/WC500196065.pdf(accessed 07/01/2015)
- European Medicines Agency. PRIority MEdicines (PRIME). http://www.ema.europa.eu/docs/en_GB/document_library/Presentation/2015/11/WC500196320.pdf(accessed 07/01/2015)
- Kenny M. EMA Defends PRIME's Early Entry Advantage For Smaller Companies. The Pink Sheet, 2016.
- Aggarwal SR. A survey of breakthrough therapy designations. Nature biotechnology. 2014; 32(4):323-330.
- Mestre-Ferrandiz J, Sussex J and Towse A. The R&D Cost of a New Medicine. OHE, London: Office of Health Economics, 2012.
- DiMasi J. New Estimates of R&D Costs: Methods and Results. Presentation at ISPOR 20th Annual International Meeting, Philadelphia, 2015.