FDA publishes latest data on RWE use in drug and biologic submissions

A year-on-year comparison shows increased uptake of real-world evidence (RWE) protocols, particularly in biologics, and the growing use of observational studies in postmarketing commitments.

The US Food and Drug Administration (FDA) has released its second annual summary of how real-world evidence (RWE) is being used to support regulatory decision-making for drugs and biologics, covering Fiscal Year (FY) 2024. The report, which includes submissions to both the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER), reveals sustained interest in RWE across the product lifecycle, especially for postmarketing commitments. It forms part of the agency’s Prescription Drug User Fee Act (PDUFA VII) commitment to enhance transparency around RWE and aligns with broader efforts to integrate real-world data (RWD) into drug development.

Modest increases at CDER, sharp growth at CBER

Across both centers, the FDA received more RWE protocol submissions in FY 2024 than in the previous year, with particularly notable growth in CBER.

While CDER's numbers remained stable, CBER more than tripled its RWE protocol submissions and supported its first approvals using RWE. Both centers received five final study reports fulfilling postmarketing requirements (PMRs) or postmarketing commitments (PMCs), a category that was not reported in FY 2023.

CDER: more safety-focused protocols, fewer RWE-supported approvals

CDER received 11 RWE protocol submissions in FY 2024, compared with 10 the previous year. The majority continue to focus on safety (9 in both years), with a slight increase in effectiveness-focused studies (1 to 2). Notably, 9 protocols support PMRs in FY 2024, an increase from 6 in 2023, whilst PMCs fell from 4 to 2.

The FDA update shows that more protocols leverage electronic health records (EHRs) (4, up from 3 in 2023) and medical claims data (7, up from 6), while registry use declines (1, down from 3). Three submissions use other data sources, including patient-level data from publications and national death records, which was not observed the previous year.

In FY 2024, CDER reviewed just 1 NDA/BLA that was based “at least in part” on RWE: the February 2024 approval of Aurlumyn (iloprost) for the treatment of severe frostbite in adults.

The CDER also reviewed five final study reports related to PMRs/PMCs in FY 2024, which were all safety-focused, non-interventional studies. Most used claims (4) and EHR (2), with some reports using registry or other data sources.

CBER: RWE adoption scales up rapidly

One notable observation is CBER's use of RWE, which expanded in FY 2024, with 15 new protocol submissions, a number nearly four-times that in FY 2023. Of these, 12 are safety-focused and three assess effectiveness. Ten protocols support PMRs, compared with just 2 the previous year.

The report also highlights the increasing use of EHR data in protocol submissions (8 submissions), while use of registries (7) and claims (5) also increased. All protocol submissions are based on non-interventional study designs.

Importantly, CBER reviewed 2 BLAs using RWE to support effectiveness. One of these was LENMELDY (atidarsagene autotemcel), a gene therapy approved in March 2024 for children with metachromatic leukodystrophy (MLD) that used an external control natural history cohort of untreated children with MLD to serve as the control group for comparison.

CBER also received 5 final PMR/PMC study reports in FY 2024, with the primary focus on safety and effectiveness endpoints.