In various therapeutic areas where life expectancy is low, delayed market access to effective medicines has highlighted the need for expedited responses by regulators to support timely access to such priority medicines. The Priority Medicines Scheme, or PRIME, was implemented by the European Medicines Agency (EMA) to support and accelerate medicine development that targets unmet medical needs. It enhances interaction and early dialogue with developers of promising medicines. The goal is to optimize development plans, expedite evaluation processes, and enable these medicines to be made available to patients sooner. Medicines that are granted PRIME accelerated assessment eligibility status during the marketing authorization application process.
Through early engagement and scientific advice, PRIME strives to enhance the generation of scientific evidence, ensuring that the data obtained is suitable for a medicine’s marketing authorization application (MAA) evaluation. Additionally, this approach helps ensure that patients are only involved in necessary clinical trials that are designed to generate the required data, optimizing the utilization of limited resources.
The EMA evaluates various factors such as chosen models, pharmacodynamic effects, safety signals, and clear presentation of analyses when granting PRIME eligibility. If providing convincing nonclinical data is challenging, the presence of clinical data becomes crucial for obtaining PRIME status. If a convincing nonclinical argument is not feasible, the presence of clinical data becomes crucial in granting PRIME eligibility.
The main benefits for applicants under the PRIME scheme include:
- Early designation of CAT or CHMP rapporteur
Within one month of being granted PRIME eligibility, applicants gain the advantage of having a rapporteur appointed early on. This rapporteur offers technical and scientific guidance throughout the MAA process.
- Initiation meeting with the rapporteur and multidisciplinary team of experts Approximately three to four months after receiving PRIME eligibility, a meeting takes place involving the rapporteur and a diverse group of EMA experts or the European medicines regulatory network. The purpose of this meeting is to discuss the overall development plan, future scientific advice, and regulatory strategy.
- Assignment of PRIME Scientific Coordinator
Promptly after receiving PRIME eligibility, applicants are assigned a dedicated point of contact known as the PRIME Scientific Coordinator. This coordinator manages all the support provided through the PRIME scheme.
- Iterative scientific advice
Throughout the entirety of the development process, applicants are afforded the chance to seek scientific advice regarding their crucial development plans and key issues. This includes the possibility of involving additional stakeholders such as health technology assessment (HTA) bodies, patients, and the FDA.
- Expedited follow-up scientific advice
Based on specific criteria, applicants may receive expedited follow-up scientific advice with shortened timelines. This allows for increased flexibility and faster response for related procedures.
- Preparation meeting for submission
Around one year before submitting the MAA, a meeting is scheduled to address various topics, including the current development status and maturity of the dossier, the type of application (e.g., conditional marketing authorisation application), plans for generating post-marketing evidence, and potential regulatory challenges.
- Confirmation of potential accelerated assessment
Upon submitting the MAA, applicants receive a higher level of certainty regarding the assessment timelines, particularly for accelerated assessment .
Application Process for PRIME Designation
The PRIME program allows sponsors involved in the early stage of clinical trials to seek PRIME designation. To qualify, they must possess the potential to address an unmet medical need (proof of concept) and initial clinical evidence demonstrating the promising activity of the medicinal product.
However, applicants from the academic sector and micro-, small-, and medium-sized enterprises (SMEs) have the opportunity to apply at a previous stage of development under specific circumstances. These circumstances include having compelling non-clinical data in a relevant model that showcases promising activity (proof of principle), as well as first-in-human studies indicating adequate exposure for the desired therapeutic effects and tolerability. This earlier entry stage is referred to as Early Entry PRIME designation.
For SMEs, it is necessary to register with the Agency’s SME office before submitting an eligibility request. If applicants believe they fall under the definition of the academic sector, they should seek clarification from the Agency before submitting an eligibility request. Further data will be required to support the granting of full PRIME designation.
An important aspect of the PRIME evaluation process is the active involvement of patients through consultations and reviews of medicine overviews, package leaflets, and safety communications. The inclusion of patient perspectives provided valuable insights during the evaluation process. Furthermore, industry surveys advocated for extending PRIME eligibility to all companies, not just SMEs, and expanding PRIME to cover post-authorisation additional indications .
Analysis of 2016 – 2021 period
EMA conducted the analysis of the first 5 years of the PRIME scheme to identify areas of improvement that would support products under the scheme. For a significant proportion of PRIME medicines, for which an MAA was submitted and had begun their accelerated assessment, roughly 56% of these products came back to the standard timetable. This demonstrates that there is the need to enhance current interactions to support necessary knowledge acquisition during development in order to facilitate accelerated assessment .
Comparing EMA PRIME to the US FDA Breakthrough Therapy Designation
The Breakthrough Therapy designation is the US FDA’s process that expedites the development and review of medicines intended to treat serious conditions. Indeed, the preliminary clinical evidence should demonstrate that the medicine offers a significant improvement compared to already available therapies in terms of clinically significant endpoints.
Both PRIME and Breakthrough Therapy Designation offer similar advantages, including early and continuous communication with EMA and US FDA respectively. Sponsors gain access to guidance, a dedicated contact point, and scientific advice fostering a collaborative approach. PRIME applications provide opportunities for regulatory strategy discussions, while Breakthrough Therapy Designation offers frequent meetings and the potential for priority review and accelerated approval .
To qualify for PRIME, a medicine must target significant public health conditions, address unmet medical needs, and demonstrate a significant therapeutic advantage over existing treatments. Breakthrough Therapy Designation requires the medicine to target serious conditions and show a significant improvement compared to available therapies, based on clinically significant endpoints.
Timelines for Applications
PRIME applications are encouraged during the exploratory clinical trials phase, while Breakthrough Therapy Designation applications are ideally submitted with or after the Investigational New Drug (IND) application. The EMA provides a decision on PRIME applications within 40 days of the review start, while the FDA responds to Breakthrough Therapy Designation applications within 60 days of receipt.
Both PRIME and Breakthrough Therapy Designation grant sponsors more opportunities to engage with regulatory officials, facilitating the development and approval process. For drugs granted Breakthrough Therapy Designation, average approval times were significantly shorter, with approvals occurring approximately three and a half years earlier compared to other accelerated approvals.
The PRIME support scheme has shown a positive impact on MAAs, with a significant number of PRIME products receiving accelerated assessment and positive CHMP opinions. Effective communication, early identification of stumbling blocks, and patient involvement play crucial roles in shaping the development and approval of innovative medicines through PRIME.
However, challenges such as switching to the normal timetable and quality-related objections for ATMPs need to be addressed to further optimize the PRIME evaluation process. Overall, the analysis underscores the importance of carefully considering available data, presenting convincing arguments, and utilizing PRIME support effectively to enhance the chances of successful marketing authorisation and addressing unmet medical needs.
For references and further reading:
- EMA. PRIME: priority medicines. European Medicines Agency. 2023
- EMA. European Medicines Agency Guidance for applicants seeking access to PRIME scheme. European Medicines Agency, 2023
- EMA. PRIME: Analysis of the first 5 year’s experience. European Medicines Agency, 2022
- US FDA. Breakthrough Therapy. United States Food and Drug Administration. 2018