The Timing and Characteristics of Supplemental Indications for Medicines.

OBJECTIVES: We investigated the timing of supplemental indications and characteristics of those approved after 9 years (small molecules) or 13 years (biologics) post initial approval across all therapeutic areas. STUDY DESIGN: Using FDA databases, we identified small molecule drugs (n = 97) initially approved between 2004 and 2015 and biologics between 2004 and 2011 (n = 21), allowing for at least 9 and 13 years of follow-up, respectively. METHODS: We reviewed drug labels as of 2024 to identify supplemental indications. We characterized supplemental indications approved at least 9 or 13 years post approval in several ways: by FDA expedited review pathway, whether they had orphan designation, whether they were approved for pediatric or geriatric populations, and their therapeutic class. We calculated the mean time between consecutive indications for small molecules and biologics. RESULTS: Overall, 24.0% of small molecule supplemental indications were approved at least 9 years post approval, and 10.0% of biologic supplemental indications were approved at least 13 years post approval. Of the supplemental indications approved (whether for small molecules or biologics) at least 9 or 13 years after initial approval, 56.9% received at least 1 FDA expedited review, 39.2% had orphan status, 49.0% were approved for pediatric use, and 62.7% were approved for older adults. The mean time between consecutive indications was longer for small molecules than for biologics (4.0 vs 3.3 years). CONCLUSIONS: Additional drug indications approved after 9 years for small molecules and 13 years for large molecules are not uncommon. Many of these later-approved indications receive expedited or orphan designation and target populations with high unmet medical needs.