Objectives: The aim of our study was to understand the current status and trends of the Breakthrough Designation (BTD), PRIME and SAKIGAKE expedited review programs regarding number of reviews, most benefited therapy areas, drugs reviewed, profile of applicants and time to regulatory approval.
Methods: We reviewed published literature, news articles, press releases and data published by the Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the Pharmaceuticals and Medical Devices Agency (PMDA) released since the launch of the expedited review programs until the end of 2018.
Results: As of 16th January 2019, we identified 326 expedited review designations across the three regulatory agencies (FDA=78% EMA=15%, MHLW=7%). The acceptance rate appears to be higher with the FDA (35%) than with the EMA (22%) and the PMDA (14%, data from 2015). The FDA has been granting a steadily increasing number of BTDs since the start of the program, in 2012. The MHLW more than tripled its granted designations in 2018 compared to 2017 (11 vs 3), while the EMA might granted less PRIME designations in 2018 than 2017 (19 vs 14). Regarding the most benefited therapy areas, oncology and rare non-cancer diseases make up two thirds of the designations. Oncology designations make up nearly half of the BTDs, but less than a third of PRIME and SAKIGAKE designations. In opposite, rare non-cancer indications make up a higher share of PRIME (31%) and SAKIGAKE (25%) than BTDs (12%). Interestingly, despite the overall low number of designations granted compared to the FDA, the EMA granted a substantial share of the designations in haematology/haemostasis (68%), while the PMDA granted more than half of the designations in Cardiovascular disease (57%). Regarding drugs that received expedited review designations, only two drugs have received BTD, PRIME and SAKIGAKE designations, but none have received regulatory approval yet (one has been submitted for regulatory submission in the three geographies). Only 9% of the drugs were granted an expedited review by at least two agencies. 38% of the expedited review designations are held by small and medium-sized enterprises (SMEs), but one third of all designations appear to be currently held by less than 5% of pharmaceutical companies/groups. 108 designations have already led to regulatory approvals, mostly by the FDA and with median of 6.1 months from filing to approval.
Conclusions: SMEs developing drugs for oncology and rare diseases could consider applying for expedited review programs, as these comprise most of the designations granted to date. The PRIME and SAKIGAKE programs appear to encompass a broader range of therapy areas, while the BTD program has been considerably focused in oncology. Few drugs obtain expedited review designation by more than one agency, which might be explained in part by the SME nature of nearly half the companies applying for the designations. Nonetheless, these data highlight the importance of having expedited review programs in the main pharmaceutical markets, in order to allow drugs with high therapeutic advantage for areas with high unmet need to efficiently reach the market. The BTD, PRIME and SAKIGAKE designations can considerably shorten the approval timeline of a drug by nearly half (11-12 vs 6.1 months), especially in the case of fatal indications with high unmet need. This is particularly relevant in the context of regulatory strategy in the US, where the FDA only discloses BTDs for drugs that have already been approved, and only on a quarterly basis.

An overview of the current status and trends in the Breakthrough Designation, PRIME and SAKIGAKE expedited review programs

DIA Europe 2019

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