Abstract:
Clinical development pipeline in weight management is expected to grow by 11/12% YoY (Year-on-Year) with more than 120 drugs at different stages of clinical development and a 64% PTSR1 (Phase Transition Success Rate) from phase II to III. Moreover, we expect that the number of patients needed to enroll for the transition from phase II to phase III in clinical trials in next years will increase substantially to from 30,000/40,000 in 2024 140,000/180,000 in 2026/20272. This substantial x20 increase in studies’ sample size is caused by the transition from a median sample size of 250/260 patients in a standard phase II dose-finding study to at least 4,500 patients studies in phase III, to comply with the FDA Guidance for Industry requirements3, of a recommended sample size of 3,000 patients randomized to the investigational drug to assess safety and no fewer than 1,500 patients on placebo for at least 1 year of treatment at the maintenance dose.
The FDA guidance also recommends (row 238-239: “subjects are expected to reflect”) that the subjects population reflects the population likely to use the drug in clinical practice with regard to age, sex, race, and ethnicity in the U.S. population. However, until recently the FDA has not provided guidance on how such populations might be defined. This is addressed in FDA draft guidance released in June 2024, which requires sponsors to develop Diversity Action Plans to improve enrollment of underrepresented populations in clinical studies. The FDA generally recommends, whenever possible, Sponsors use estimated US disease prevalence or incidence by demographic characteristic from publicly available data sources (e.g., published literature, publicly available epidemiological surveys, certain registries) to inform enrollment goals. However, this information may not exist for many conditions or may be many years out of date. In recent years, large electronic health record (EHR) databases have been created that enable the rapid assessment of demographic data from millions of US healthcare consumers based on International Classification of Diseases (ICD) codes for medical conditions. These real-world data (RWD) provide an opportunity to readily define the demographic characteristics of patient populations and have been proposed for common conditions such as Alzheimer’s disease, but not obesity. To determine the demographic distribution (age, sex, race and ethnicity) of individuals living in the US with a diagnosis of obesity for clinical trial planning purposes, we used RWD collected from the TriNetX Network, which provides access to electronic health records (EHRs) (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 150 million individuals across approximately 80 healthcare organizations (HCOs) in the US. . Using a combination of new ICD-10-CM E-codes for adult obesity (E66.811, E66.812, and E66.813) together with existing Z-codes for BMI ≥25 Kg/m2) per recent Centers for Disease Control guidance, and excluding codes for hypofunction and other disorders of the pituitary gland or Cushing’s syndrome or bariatric surgery, we identified 165,610 individuals. The demographic distribution was 66.7% Female, 33.3% Male, 69.3% White, 19.2% Black or African American (BAM), 2.4% Asian, 9.2% other/unknown Race, 74.2% Non-Hispanic or Latino, 9.1% Hispanic or Latino (HL) and 17.0% other/unknown ethnicity. Based on an analysis of binomial confidence intervals, a hypothetical US trial phase III obesity clinical trial of 4 500 patients would be statistically representative (p <.05) of the EHR-derived population if it included a range of 2939-3064 Females, 1435-1560 Male, 3057-3180 White, 811-915 BAM, 88-129 Asian and 357-433 HL subjects.
- Clinical Development Success Rates and Contributing Factors 2011–2020, © BIO | QLS Advisors | Informa UK Ltd 2021.
- Internal data elaboration by the Authors
- FDA. (2025). Obesity and Overweight: Developing Drugs and Biological Products for Weight Reduction Guidance for Industry Obesity and Overweight: Developing Drugs and Biological Products for Weight Reduction Guidance for Industry. January.
