165: Demographic Composition of New Molecular Entities Approved by the United States FDA Between 2017 & 2023 to Treat Type 2 Diabetes

Statement of Purpose, Innovation or Hypothesis: In the U.S., type 2 diabetes mellitus (T2DM) affects about 13% of the population, with a higher incidence and/or prevalence in some racial and ethnic minority populations (e.g., American Indian or Alaskan Native (AIAN), Native Hawaiian or Other Pacific Islander (NHOPI), Black or African American (B/AA), Asian, and Hispanic or Latino) as well as adults over 65 years (Table 1). Differences in management and outcomes have also been reported for some populations (PMID:32413037 and 30233490). In this study, we aimed to: (1) characterize the demographic enrollment patterns for therapeutic products approved by the Food & Drug Administration (FDA) to treat T2DM between 2017 and 2023, (2) compare enrollment with the prevalence of the disease for the selected demographic populations, (3) evaluate if any exposure and/or response differences had been reported in the FDA approved product labeling, and (4) investigate if any postmarketing requirement and commitment (PMR and PMC) studies were established for the selected demographic populations.

Description of Methods & Materials: Novel New Drug Applications (NDAs) and Biologic License Applications (BLAs)) approved by CDER, FDA between January 2017 and December 2023 to treat T2DM were identified. The product labeling, regulatory review documents, and approval letters were extracted from Drugs@FDA. Using applicant submitted information internal to the FDA, phase I - III trials supporting the therapeutic product applications were identified and information such as trial name, trial phase, and subject-level demographic information for race, ethnicity, sex, age, and geographic location were collected. Descriptive statistical analysis was performed using JMPv16. Participation-to-Prevalence Ratio (PPR; i.e., percentage of the demographic among trial participants/percentage of the demographic among disease population) was calculated.

Data & Results: Overall, 59,586 participants had demographic data available from 125 clinical trials for 6 NME applications (Table 1 and Figure 1). Of this, 76.5% (n= 45,573) participants were from outside the U.S. and were from about 70 countries. Overall, participants were mostly White, 73.8% (n= 43,984), Not Hispanic or Latino, 73% (n= 43,497), male 61.5% (n=36,634), and 18-64 years old, 55.3% (n= 32,918). Racial and ethnic minority populations such as NHOPI, AIAN, and B/AA represented 0.2% (n=144), 2.7% (n=1,628), and 5.1% (n= 3,018), respectively. Overall, 38.5% (n= 22,952) were female. PPR information is shown in Table 1.  No exposure differences were reported for the analyzed subpopulations, while 3 drugs reported increased incidence of some adverse events in older adults. Four NMEs had PMRs for studies in pediatric patients 10-17 of age.

Interpretation, Conclusion or Significance: Based on PPR, racial and ethnic minority populations such as NHOPI, AIAN, and B/AA as well as older adults continue to be under enrolled when compared to their disease prevalence. Though women were not under enrolled when compared to the disease prevalence, the average representation (38.5%) was lower than men. Limitations of the PPR analysis include that data from both U.S. and outside of U.S. were utilized and the timeframe are not completely synchronous between trial population enrollment and prevalence data collection. Based on the available data, no safety and/or efficacy concerns were identified that necessitated dose modifications or additional monitoring recommendations for the selected demographic subpopulations.

Disclosures: The views expressed are those of the authors and do not reflect official policy of the FDA.

Citations/References: Mathur R, Farmer RE, Eastwood SV, Chaturvedi N, Douglas I, Smeeth L. Ethnic disparities in initiation and intensification of diabetes treatment in adults with type 2 diabetes in the UK, 1990-2017: A cohort study. PLoS Med. 2020 May 15;17(5):e1003106. doi: 10.1371/journal.pmed.1003106. PMID: 32413037; PMCID: PMC7228040. Caballero AE. The "A to Z" of Managing Type 2 Diabetes in Culturally Diverse Populations. Front Endocrinol (Lausanne). 2018 Aug 28;9:479. doi: 10.3389/fendo.2018.00479. PMID: 30233490; PMCID: PMC6127640.

Additional Information/Authors: N/A