The PRIority MEdicines (PRIME) scheme is an initiative from the European Medicines Agency (EMA) designed to provide early and enhanced support to drug developers for promising new medicines that address significant unmet medical needs. This scheme is intended to accelerate the development and availability of innovative therapies in the European Union (EU), while maintaining rigorous standards of efficacy and safety.

The PRIME scheme was launched in 2016 to facilitate an early, proactive dialogue between applicants and the EU regulatory network, ensuring the generation of a robust data package to address marketing authorization application requirements and enable accelerated assessment of new medicines targeting an unmet medical need.

The Regenerative Medicine Advanced Therapy (RMAT) designation is for advanced therapies intended to treat life-threatening conditions and preliminary clinical evidence indicates the therapy has the potential to address unmet medical need.

The PRIME scheme is limited to medicines under development which are not authorized in the EU and for which the applicant intends to apply for an initial marketing authorisation application (MAA) through the centralized procedure. The eligibility criteria for PRIME are identical to EMA’s MAA accelerated assessment criteria but are applied at an early stage of development with a higher degree of uncertainty compared to the time of accelerated assessment requests.

Eligibility for the PRIME scheme considers both the magnitude of treatment effect and the clinical relevance of observed outcomes that predict effects on morbidity, mortality, or disease progression.

Products eligible to PRIME support shall:

• Target conditions where there is an unmet medical need, i.e., for which there exists no satisfactory method of diagnosis, prevention, or treatment in the Community or, even if such a method exists, in relation to which the medicinal product concerned will be of major therapeutic advantage to those affected.
• Demonstrate the potential to address the unmet medical need to a significant extent, for example, by introducing new methods of therapy or improving existing ones.
• Have the potential to provide a significant therapeutic advantage to patients with a specific medical condition based on available data and clinically meaningful outcomes.
• Provide evidence of clinical response in patients, substantiated by exploratory clinical studies addressing an unmet medical need.
• PRIME is not suitable for products that are in advanced stages of development, in the pre-submission phase of an MAA, or already authorized in the EU with a new indication being sought.

The drugs or products must address an unmet medical need and target a seriously debilitating or life-threatening disease or a rare disease, or they must be intended for use in emergencies in response to a public health threat. It is important to emphasize that the expedited pathways will not lower the bar for approvals, and the intention is to deepen the partnership between the authorities and the drug developing companies. These interactions will provide generating the most relevant data and it will allow Health Authorities to prioritize the review of applications for drugs that may be crucial for patients with serious conditions.

In its guidelines, the EMA recommends that the applicant applies for PRIME while in the exploratory clinical trial phase and can demonstrate proof of concept that the investigational drug works. Micro, small, and medium-sized enterprises, and academic research may qualify for PRIME designation at an earlier stage of development if they have compelling non-clinical data in a relevant model provide early evidence of promising activity (proof of principle) and first-in-human studies indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability. In addition, PRIME support may be withdrawn if emerging data indicate that the criteria no longer apply. The CHMP will grant or deny PRIME designation within 40 days of the start of the PRIME application assessment.

Still, an acceptance of the scheme does not guarantee fast approval or approval at all.

One of the main benefits of PRIME for drug developing companies is the potential for accelerated assessment, which can help to expedite the regulatory approval process and bring new treatments to patients more quickly. Another is the early and ongoing regulatory support provided by the EMA, including access to scientific advice, guidance on the overall development plan, and the opportunity to engage with relevant EMA committees and working parties.

If we break down the key benefits, the drug developers are entitled to:

• Early appointment of a CHMP/CAT Rapporteur: Request for the appointment of a Rapporteur from the CHMP or CAT as early as possible in the development process to ensure continuity in the life-cycle approach.
• Kick-off meeting with the CHMP/CAT Rapporteur and a multidisciplinary group of EMA experts to provide preliminary guidance on the overall development plan and discuss key development steps, and the recommended regulatory strategy.
• A PRIME Scientific Coordinator, who will serve as a dedicated point of contact and coordinate the support offered throughout the scheme.
• Iterative scientific advice on the overall development plan at major development milestones and on key issues with the possibility to involve additional stakeholders such as health technology assessment (HTA) bodies, patients, and the US FDA.
• Access to expedited follow-up scientific advice under certain criteria with shortened timelines for receiving the adopted CHMP advice.
• A submission readiness meeting approximately one year before the MAA filing date to discuss the status of the development for key development areas, the maturity of the dossier, and plans for post-marketing evidence generation and any expected regulatory challenges.
• A dedicated toolbox to support the quality data package development.

By engaging with the regulatory authorities early on, medicine developers can benefit from early

dialogue, interaction, and proactive support, leading to faster reviews and reduce the risk of delays or setbacks in the approval process.

At NDA, we have experience of PRIME assessments from both client and agency perspective. Drop us a line by using the form below and find out how we can be of help.