Presentation (CTI)

OBJECTIVES: This study aimed to assess the extent of regulatory concordance and divergence in expedited oncology approvals among the FDA (Food and Drug Administration), EMA (European Medicines Agency), TGA (Therapeutic Goods Administration), and PMDA (Pharmaceuticals and Medical Devices Agency) between 2019-2023, by analyzing alignment in approval pathways, clinical evidence components, and review timelines.
METHODS: We retrospectively analyzed 40 oncology drug-indication pairs granted first-time expedited approval. Using the FDA’s first approvals as a reference, we assessed pathway alignment (expedited vs. standard), analytical concordance (analysis population, primary endpoint, data cut-off date), and submission and approval timelines based on publicly available regulatory documents. Concordance was calculated for each agency using shared approvals, and analyzed through descriptive and comparative statistics.
RESULTS: Among the 36 FDA-led first-time expedited approvals, EMA, TGA, and PMDA subsequently approved 24, 18, and 12 drug-indication pairs, respectively. The TGA exhibited the highest concordance with the FDA, granting expedited approval in 72% (13/18), and achieving full alignment in both pathway and analytical components in 28% (5/18), despite submission delays (IQR:135-540 days). The EMA granted expedited approvals in 71% (20/28), but demonstrated analytical divergence: of 24 cases sharing same trial, 88% (21/24) extended the data cut-off date, and 67% (16/24) used different analysis populations. Although submission intervals were relatively short (IQR:0-35 days), EMA’s review time was significantly longer than the FDA’s (median 384 vs.168 days; p<0.01). The PMDA showed the lowest concordance, with only 8% (1/12) aligned on the pathway, and analytical divergence largely driven by requirements for Japanese population data, and submission delays (IQR:135-615 days). Across agencies, submission delays were strongly correlated with approval delays (ρ=0.83-0.98, all p<0.05).
CONCLUSIONS: Significant divergences persist across regulatory agencies in expedited oncology approvals, particularly in analytical approaches and timelines. Harmonizing evidentiary standards and reducing submission lags may enhance global alignment and access to innovative cancer therapies.