Since the PRiority MEdicines (PRIME) program scheme was introduced two years ago, more than 40 products have been granted PRIME designation.1 In August 2018, the first two therapies with PRIME designation were granted marketing approval by the European Commission (EC) – Novartis’s Kymriah (tisagenlecleucel) and Kite Pharma/Gilead’s Yescarta (axicabtagene ciloleucel).
Yescarta and Kymriah are both groundbreaking chimeric antigen receptor (CAR) T-cell therapies that harness the immune system to target hematological malignancies. Both target the B-cell cancer marker CD19. Yescarta is indicated for two types of non-Hodgkin lymphoma (NHL), while Kymriah is for B-cell precursor acute lymphoblastic leukemia (B-cell ALL) and one type of NHL.2,3
Faster patient access
The aim of the PRIME program when it was introduced by the European Medicines Authority (EMA) in March 2016 was to smooth the regulatory pathway and provide faster patient access to drugs providing significant advantage over existing therapies, or for serious conditions where there are currently no treatments available. While companies of any size can benefit from the scheme, the designation is especially targeted toward small and medium enterprises and academic institutions, to help compensate for any lack of experience in the regulatory arena, compared with large companies. For larger companies, application is based on preliminary evidence of clinical benefit, while smaller companies and academic institutions can apply for the designation earlier in the development process, on the basis of promising preclinical data and clinical tolerability.4
“The aim of the PRIME program … was to smooth the regulatory pathway and provide faster patient access to drugs providing significant advantage over existing therapies, or for serious conditions where there are currently no treatments available.”
Candidates selected for PRIME gain access to specific guidance and support in development planning and regulatory approach. Successful applicants gain early access to a rapporteur from the EMA’s Committee for Medicinal Products for Human Use (CHMP) or from the Committee on Advanced Therapies (CAT). An initial kick-off meeting is conducted with the rapporteur and a multidisciplinary group of experts from relevant EMA scientific committees and working parties. A dedicated contact within the EMA is assigned, and scientific advice is provided at key milestones. PRIME therapies would also expect to gain Accelerated Assessment status, although this is not guaranteed.4
Figure 1: Timelines of U.S. and E.U. approval for Yescarta and Kymriah. Source: Cortellis Regulatory Intelligence, Clarivate Analytics.
It is very early days for the PRIME designation, and thus difficult to assess the future overall benefit and success of the scheme. PRIME designation was introduced for medicines that show significant advantages over existing treatments or meet an unmet medical need – criteria that both Yescarta and Kymriah fulfill. Part of the stated aim of the PRIME designation is to “optimise development plans and speed up evaluation.”4 In this case, however, although the developers of both drugs received regulatory advice and support during development, when it came to the point of regulatory assessment for these first two drugs to be approved under the PRIME program, neither received the accelerated assessment they would have expected. In addition, although the trial designs were accepted for European regulatory approval, they were not initially considered sufficient for granting reimbursement in the UK.
Equalize the opportunities
At this early juncture, it is difficult to say whether the PRIME designation is meeting its objective of providing faster access for patients to new medicines. Certainly, in the U.S., the time taken between filing and approval was considerably less – 209 versus 294 days for Kymriah, and 390 versus 201 days for Yescarta. However, this is generally the case and it could be argued that the approval process for Kymriah has been accelerated given the complex nature of the drug and considering the median 383 days review time for EMA-approved drugs.5
“It is possible that one of the overall benefits of the PRIME program will be to equalize the opportunities between the very large well-established pharmaceutical companies and the smaller, less-experienced commercial entities and academics.”
It is possible that one of the overall benefits of the PRIME program will be to equalize the opportunities between the very large well-established pharmaceutical companies and the smaller, less-experienced commercial entities and academics. It will be very interesting to follow the progress of the other drugs currently partaking in the PRIME program.
This article was adapted from a longer analysis by the author and colleagues of the progress of Kymriah and Yescarta under PRIME.