(206) The timing and characteristics of supplemental indications for small and large molecule medicines

Background: : The Inflation Reduction Act (IRA) Drug Price Negotiation Program (DPNP) aims to reduce prices for certain drugs but subsequently introduces disincentives for companies to pursue supplemental indications, especially as medications approach the effective date for the Maximum Fair Price (MFP) – nine years for small molecules and thirteen years for biologics.

Objective: : We investigated the number and characteristics of supplemental indications approved ≥9 (small molecules) or ≥13 years (biologics) post-initial approval across all disease areas and drug types.

Methods: : Using the Food and Drug Administration (FDA) databases, we identified brand-name small molecule drugs initially approved between 2004-2015 and biologics approved between 2004-2011, allowing at least 9 and 13 years of follow-up, respectively. We reviewed each drug’s label as of 2024 to identify supplemental indications. We characterized supplemental indications approved ≥9 years or ≥13 years post-approval by FDA expedited review pathway; whether it had an orphan designation; whether it was approved for pediatric and geriatric populations; and its therapeutic class.

Results: : In our sample of 250 supplemental indications, 24.2% of 182 small molecule supplemental indications were approved ≥9 years post-approval, while 10.3% of 68 biologic supplemental indications were approved ≥13 years. Of the 51 supplemental indications approved (regardless of small molecule or biologic) ≥9 or ≥13 years after initial approval, 56.9% received at least one FDA expedited review designation (59.1% for small molecules vs. 42.9% for biologics), 39.2% had orphan status (36.4% vs. 57.1%), 49.0% were approved for pediatric use (50.0% vs. 42.9%), and 62.7% for older adults (61.4% vs. 71.4%). The most common therapeutic areas for supplemental indications for small molecules were oncology (34.1%), infectious disease (15.9%), and circulatory disease (9.1%); for biologics they were oncology (28.6%), musculoskeletal disease (28.6%), and circulatory disease (14.3%).

Conclusions: : We found that a sizeable proportion of supplemental indications were approved many years after a drug’s first approval , and many of these longer-term supplemental indications received expedited or orphan designations and addressed high-need populations, including children, older adults, and patients with cancer, infectious disease, and cardiovascular diseases. Our finding further suggests that DPNP may disproportionately impact small molecules, as their supplemental indications were developed over longer timelines and more likely to be approved after the MFP effective time.

Sponsorship:: Eli Lilly and Company