Presentation (CTI)

OBJECTIVES: Currently, 44% of ongoing phase 3 industry-sponsored trials are conducted outside the United States (US). This study aims to evaluate whether clinical data with very low or no representation of US patients can sufficiently support the US Food and Drug Administration (FDA) approval.
METHODS: FDA drug approvals in 2023 and 2024, with less than 5% of US patients in pivotal trials, were identified and analysed, and compared with similar approvals in 2017.
RESULTS: In 2023 and 2024, 5 (9%) and 11 (22%) novel drugs, respectively, were approved by the FDA, based on trials with less than 5% US patient participation. These trials were primarily conducted in multi-national, non-US settings. In 2017, only 2 (4%) novel drugs met the criterion, including Radicava, evaluated exclusively in Japan with no US patient representation. In 11 cases (61%), consistent outcomes across racial and ethnic subgroups, as well as similar pathogenesis and disease course across populations, were sufficient to address representativeness of foreign studies for the US populations. For Radicava, an ethnic bridging analysis was conducted to assess factors potentially differentiating outcomes in the Japanese and US patients. However, in other cases, post-marketing studies were required to confirm representativeness: further analyses of ethnic and racial groups in 4 cases, 5-year surveillance studies in the US for 2 cases and a clinical trial with US patients in 1 case. High unmet medical needs were indicated for 16 of 18 submissions (89%), primarily due to severe disease or lack of effective treatments.
CONCLUSIONS: Cases show an increasing rate of products accepted based on foreign data. If studies are conducted under Good Clinical Practice (GCP) and there are no significant regional or ethnic differences in outcomes, they could be accepted without further requirements. However, sometimes post-marketing studies are needed, and recent US policy changes could increase the FDA’s foreign data scrutiny.