After two years from the launch of the EMA’s PRIority Medicines scheme (PRIME), the European Medicines Agency published a report discussing its current state of implementation and opportunities to further ameliorate procedures to support and optimise development and reach a fast approval of innovative medicines for unmet medical needs. EMA also published an updated version of the guidance document on PRIME, questions and answers and the template for applicants’ requests.

Early dialogue and regulatory support

The first three applications for marketing authorisation of new products developed under the PRIME scheme are currently under evaluation by EMA and are expected to gain opinion during 2018. Central to the PRIME scheme is the reinforcement of early dialogue and regulatory support to the industry. Since 2016, EMA has accepted just 36 (21%) of the total 177 applications received for eligibility to the PRIME scheme. The medium number of applications per month (8) has kept constant during the two years of activity of the scheme.
Oncology and haematology have been the therapeutic areas more represented, together with infectious diseases, neurology and psychiatric disorders. 83% of the approved applications concern rare diseases (for example, to treat achromatopsia associated with defects in CNGB3, X-linked hypohidrotic ectodermal dysplasia, primary hyperoxaluria type 1 and osteogenesis imperfecta types I, III and IV) and 44% were targeted to paediatric patients. Two of the six requests in the field of infectious diseases and vaccines have been approved for the treatment of septic shock and chronic hepatitis D, respectively.
The majority of the approved medicines (22) also received a scientific advice from EMA; notably, many of the 37 requests for advice also contained an input from health technology assessment bodies and patients. The majority of applications referred to chemical products (42%), followed by biological products (25%) and advanced therapies (AMTPs, 25%). This last category is often developed by small and medium sized companies.
According to EMA’s report, the quality of applications received by the Agency is generally good; more than 50% of applications to the PRIME scheme came from SMEs. Just eight applications have been considered out of scope, and thus not object of review. Noticeably, the proper time for application is considered to be the proof of principle (compelling non-clinical data and tolerability data from initial clinical trials) for SME and the proof of concept (preliminar clinical evidence) for non-SME applicants. Three of the eight applications received from SMEs have been granted eligibility. 72 over the 161 total requests coming from non-SME companies referred to phase 2 data (44%), 43 to phase 1-2 (26,7%) and 35 to phase 1 (21,75%). Very few have been so far the requests related to phase 3 data (3), compassionate use or case series (3) and literature (5). Only three are the applications advanced by the academia, a sign for EMA to continue to raise awareness on the possible support the Agency may offer to universities wishing to translate academic research into novel methodologies and medicines. Other requests rejected without review related to projects not clearly falling in the category of medicinal products.

The reasons to deny eligibility

Therapeutic advantage is the key to access the PRIME scheme: products are eligible if they can demonstrate the potential to significantly address an unmet medical need, for example by introducing new methods of therapy or improving existing ones. The request referred to a certain indication has to be supported by data demonstrating such a major therapeutic advantage to patient. The justification of eligibility criteria has to be provided by applicants at the time of the application.
According to the report, the first year of activity the scheme saw 14 requests denied because of a too advanced phase of development to ask advice. This decreased to three applications in the second year. The great majority (87%) of other requests were denied due to issues with robustness of the presented data to support the significant therapeutic advantage or inconclusive/insufficient effect with respect to magnitude, duration and relevance of endpoints. In a limited set of dossiers the proposed unmet clinical need was found to be unacceptable or not sufficiently justified. The new guidance issued by EMA better explains this point, highlighting how the PRIME committee might agree that an unmet medical need may still exist in the concerned condition (e.g. in a subgroup of patients or in view of limitations of existing therapies), but this need to be clearly supported by the applicant in its request.

The kick-off meetings

Multidisciplinary ‘kick-off’ meetings are a key component of the PRIME scheme, as the give the opportunity to identify issues, share the different positions and reach an agreement on the next steps in the development of the product. They occur after two-three months from entering the scheme and after the CHMP/CAT Rapporteur has been appointed; 31 meeting have been organised so far, with the participation of rapporteurs from EMA’s CHMP or CAT and the chairs and experts of relevant Agency’s committees. The preparation and conduct of kick-off meetings is also addressed within the new guidance on interaction in the context of PRIME published by EMA.

The meetings are intended also to discuss key development steps subject of future advice and the recommended regulatory strategy supporting development of the product. HTA bodies and patients organisations might also be involved on key issues, under the coordination of EMA acting as the single contact point to provide regulatory support under the PRIME scheme. The eligible products also receive confirmation of the potential for accelerated assessment at the time of the application for marketing authorisation.

LEAVE A REPLY

Please enter your comment!
Please enter your name here