S129: Ten Year Retrospective Review and Trend Analysis of FDA Accelerated Approvals
Ernest Mario School of Pharmacy, Rutgers University United States
To analyze characteristics of FDA expedited program designations and utilize a trend analysis in relation to accelerated approval pathways over the past 10 years, including timings to approvals and therapeutic categories.
A retrospective study was conducted by the authors using the FDA’s publicly available databases of expedited programs from www.fda.gov. We analyzed 10 years of NDA and BLA data, excluding supplemental applications, from January 1, 2012 to December 31, 2021.
There were 96 original FDA accelerated approvals over the 10 year span. In 2012 (n=6), there were 6 NDA approvals and 0 BLA approvals, while in 2021 (n=18), there were 12 NDA approvals and 6 BLA approvals. In 2012 (n=6), 100% of accelerated approvals had orphan drug designation, while in 2021 (n=18), 72% had that designation. In 2012 (n=6), 67% of accelerated approvals had fast track designation, while in 2021 (n=18), 33% had that designation. In 2012 (n=6), 50% of accelerated approvals had priority review designation, while in 2021 (n=18), 61% had that designation. In 2013 (n=2), when breakthrough therapy was offered, 50% of accelerated approvals had breakthrough therapy designation, while in 2021 (n=18), 44% had that designation. In 2012 (n=6), 50% of accelerated approvals required advisory committees, while in 2021 (n=18), 11% required an advisory committee meeting. Average time to accelerated approval from submission was 8.2 months (n=96). Accelerated approvals with no designations (n=5) on average were approved in 18.0 months while applications with all 4 designations (breakthrough therapy, orphan drug, priority review, fast track) (n=12) on average were approved in 5.6 months. Over the 10 years, fast track designation (n=35) increased the time to accelerated approval by <1 month. During the same period, priority review (n=73) reduced the time to accelerated approval by 4.1 months and breakthrough designation (n=50) reduced the time by 3.4 months. The largest reduction of 4.2 months came with orphan drug designation (n=80). Drugs for non-malignant hematologic diseases (n=2) on average were approved in 5.4 months. Drugs for solid tumors (n=42) on average were approved in 7.0 months while drugs for hematologic cancers (n=30) on average were approved in 8.5 months. Novartis Pharmaceuticals Corp. received the most FDA accelerated approvals (9) over the 10 year span. Notably, holding an advisory committee meeting (n=14) increased the time to approval by 4.1 months.
Our data indicates that over the past ten years, there has been an increasing number of NDA and BLA accelerated approvals in the United States. Having certain FDA designations is beneficial for sponsors, as it reduces time to accelerated approval. Of the four designations studied, orphan drug designation may be most beneficial compared to other expedited programs in terms of shortening review times. This finding is interesting considering that it was not created to grant increased FDA interaction or support. In addition, orphan drug designation demonstrated the largest decrease in time to approval while the requirement for an advisory committee meeting notably extended the approval period. Of the various therapeutic categories studied, solid tumors and hematologic cancers have had the most accelerated approvals.
Further, the expansion of expedited FDA approval pathways has led to the overall increased utilization of these routes by sponsors. This data affirms that the expedited programs created by the FDA in recent years have a beneficial impact on access to cancer medicines. In aggregate, these pathways also have enabled more treatments to reach the market while expanding the options for patients and prescribers. Going forward, further research is indicated to continually assess these trends and the impact they have on submissions, approvals, and access.