Presentation (CTI)

OBJECTIVES: Real-world evidence (RWE) is increasingly included as supportive evidence in applications for multiple myeloma (MM) products in the US and EU. An understanding of how RWE has been used in marketing applications (eg, data types, methodologic approaches) is warranted. This study aimed to describe and characterize MM regulatory submissions leveraging RWE and contextualize major themes of regulatory feedback from FDA and EMA.
METHODS: All MM products approved by FDA and EMA between January 2021 and April 2024 were identified. FDA review documents and EMA European public assessment reports were analyzed. Written feedback on RWE contributions to marketing applications was identified directly from available regulatory review documents. Regulator comments were categorized by general themes and common characteristics and further reconciled against existing regulatory RWE industry guidance.
RESULTS: Between January 2021 and April 2024, FDA and EMA approved 21 novel/supplemental MM marketing applications. RWE was leveraged in 52.4% (n=11) of applications, all of which were indicated for relapsed/refractory MM. Approximately, 45.5% (n=5) of marketing applications leveraged Flatiron Health RWE; 27.3% (n=3) independent academic centers; 18.2% (n=2) Optum; 18.2% (n=2) prospective real-world studies; and 9.1% (n=1) COTA (non-mutually exclusive). RWE was used as an external comparator cohort (36.4%, n=4), to contextualize unmet medical need (45.5%, n=5), and to demonstrate natural history of MM (18.2%, n=2). Regulatory feedback highlighted certain clinical and treatment-related heterogeneity between the registrational trial and RWE study. Nonetheless, regulators considered descriptive RWE primarily as supportive evidence for the marketing application.
CONCLUSIONS: FDA and EMA regulators have accepted RWE as supportive evidence for marketing applications in relapsed/refractory MM. The feedback aligns well with existing regulatory guidance. This analysis highlights the significance of including RWE in future MM regulatory submissions.