TRENDS AND POSTMARKETING OUTCOMES OF ACCELERATED APPROVALS (AAS) IN FDA NEW DRUG APPLICATIONS AND BIOLOGIC LICENSE APPLICATIONS (NDAS/BLAS) FROM 1992-2025
Author(s)
Sarah Ronnebaum, PhD;
Precision AQ, Bethesda, MD, USA
Precision AQ, Bethesda, MD, USA
OBJECTIVES: To examine key factors associated with AA designations, impact on application approval time, and ultimate regulatory outcomes.
METHODS: All verified clinical benefit, ongoing, and withdrawn indications with AA from original and supplemental NDAs/BLAs between January 1992 and December 2025 were reviewed using data from the FDA and the Federal Register. Vaccines, blood products, gene/cell therapies, and different formulations or dosing for the same drug-indication pair were excluded from analysis. Relative risk (RR) was calculated for comparisons of interest.
RESULTS: Among original NDAs/BLAs, orphan indications were significantly more likely than non-orphan indications to receive AA designation (RR=2.2). Original NDAs/BLAs undergoing AA were significantly more likely than non-AA NDAs/BLAs to undergo priority review (RR=2.1). AA designation decreased FDA review time of priority applications by a mean (median) of 3.7 (0.5) months. Across original and supplemental indications, most conditional AAs were verified (60%), while 26% are currently conducting confirmatory trials and 14% were withdrawn. Among verified indications, the mean (median) time to full FDA approval was 57.0 (45.9) months between 1992-2014 but shortened to 37.8 (33.6) months between 2015-2025. Drugs that received conditional AA between 2021-2025 are currently anticipated to complete necessary postmarketing trials within 46.5 (47.4) months of their respective approvals. Among withdrawn AA indications, key reasons for withdrawal included a lack of clinical benefit (8% of all AAs), no trial being conducted (3%), safety concerns (2%), or resource reallocation (<1%), and manufacturers voluntarily requested the FDA to withdraw approval in 92% of these instances.
CONCLUSIONS: In addition to faster clinical development through the use of surrogate endpoints, AA enables shorter time to conditional approval, particularly for orphan indications. Most drugs demonstrate sufficient safety and efficacy following conditional AA. Full approval can generally be expected within four years of conditional AA.
METHODS: All verified clinical benefit, ongoing, and withdrawn indications with AA from original and supplemental NDAs/BLAs between January 1992 and December 2025 were reviewed using data from the FDA and the Federal Register. Vaccines, blood products, gene/cell therapies, and different formulations or dosing for the same drug-indication pair were excluded from analysis. Relative risk (RR) was calculated for comparisons of interest.
RESULTS: Among original NDAs/BLAs, orphan indications were significantly more likely than non-orphan indications to receive AA designation (RR=2.2). Original NDAs/BLAs undergoing AA were significantly more likely than non-AA NDAs/BLAs to undergo priority review (RR=2.1). AA designation decreased FDA review time of priority applications by a mean (median) of 3.7 (0.5) months. Across original and supplemental indications, most conditional AAs were verified (60%), while 26% are currently conducting confirmatory trials and 14% were withdrawn. Among verified indications, the mean (median) time to full FDA approval was 57.0 (45.9) months between 1992-2014 but shortened to 37.8 (33.6) months between 2015-2025. Drugs that received conditional AA between 2021-2025 are currently anticipated to complete necessary postmarketing trials within 46.5 (47.4) months of their respective approvals. Among withdrawn AA indications, key reasons for withdrawal included a lack of clinical benefit (8% of all AAs), no trial being conducted (3%), safety concerns (2%), or resource reallocation (<1%), and manufacturers voluntarily requested the FDA to withdraw approval in 92% of these instances.
CONCLUSIONS: In addition to faster clinical development through the use of surrogate endpoints, AA enables shorter time to conditional approval, particularly for orphan indications. Most drugs demonstrate sufficient safety and efficacy following conditional AA. Full approval can generally be expected within four years of conditional AA.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
HPR15
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Rare & Orphan Diseases