Characteristics of RWE used in Regulatory Decision-Making for Marketing Authorization Applications (MAAs)
Author(s)
Shivani Aggarwal, PhD, MS1, David Goldfarb, PhD, MPH2.
1Landmark Science, Inc, Los Angeles, CA, USA, 2Landmark Science, Inc, New York, NY, USA.
1Landmark Science, Inc, Los Angeles, CA, USA, 2Landmark Science, Inc, New York, NY, USA.
OBJECTIVES: Real-world evidence (RWE) is increasingly used to support regulatory decision-making. Numerous regulatory agencies including the FDA and EMA have issued guidance on evaluating RWE in MAAs, yet trends in its application in MAAs are not well characterized.
METHODS: We examined trends in RWE use and regulatory feedback on drug submissions containing RWE in MAAs from January 2021 to present, focusing on therapeutic areas, type of RWE, and common practices in submissions. Publicly available documents were extracted and reviewed. Two independent reviewers extracted and categorized the RWE. Descriptive analyses were performed to identify trends in the characteristics of drugs and of the RWE.
RESULTS: Seven medicines were analyzed: idecabtagene vicleucel (ide-cel), omburtamab, sotorasib, alpelisib, palovarotene, tacrolimus, and omaveloxolone. All medicines (100%) were orphan or ultra-orphan drugs. Three of the seven drugs (42.8%) were for oncology or hematology while the remainder (57.1%) were indicated for rare diseases. In the US, 5/7 (57.1%) were first-in-class for the respective therapeutic areas, while 2/7 (28.6%) were for additional indications. The majority (6/7) had substantial RWE in the MAAs. Trends revealed varying levels of reliance on RWE, with 4/7 (57.1%) MAAs containing externally controlled arms using real-world data. Two of the four ECAs were accepted by the FDA, of which one was post-hoc and confirmatory. MAAs for expanded indications had heavier reliance on RWE. Five MAA reviews noted either sponsor submission of patient-level data or FDA reanalyzing or evaluating the patient-level RWD. A total of 2/7 (28.6%) reviews noted FDA audits or site inspections related to the RWE/RWD submitted.
CONCLUSIONS: MAAs containing RWE submitted to the FDA were predominantly for rare diseases medicines and for first-in-class indications. Acceptability of RWE varied based on entire body of evidence. Further investigation into factors influencing RWE acceptability and its integration into MAAs across other regulators such as EMA is warranted.
METHODS: We examined trends in RWE use and regulatory feedback on drug submissions containing RWE in MAAs from January 2021 to present, focusing on therapeutic areas, type of RWE, and common practices in submissions. Publicly available documents were extracted and reviewed. Two independent reviewers extracted and categorized the RWE. Descriptive analyses were performed to identify trends in the characteristics of drugs and of the RWE.
RESULTS: Seven medicines were analyzed: idecabtagene vicleucel (ide-cel), omburtamab, sotorasib, alpelisib, palovarotene, tacrolimus, and omaveloxolone. All medicines (100%) were orphan or ultra-orphan drugs. Three of the seven drugs (42.8%) were for oncology or hematology while the remainder (57.1%) were indicated for rare diseases. In the US, 5/7 (57.1%) were first-in-class for the respective therapeutic areas, while 2/7 (28.6%) were for additional indications. The majority (6/7) had substantial RWE in the MAAs. Trends revealed varying levels of reliance on RWE, with 4/7 (57.1%) MAAs containing externally controlled arms using real-world data. Two of the four ECAs were accepted by the FDA, of which one was post-hoc and confirmatory. MAAs for expanded indications had heavier reliance on RWE. Five MAA reviews noted either sponsor submission of patient-level data or FDA reanalyzing or evaluating the patient-level RWD. A total of 2/7 (28.6%) reviews noted FDA audits or site inspections related to the RWE/RWD submitted.
CONCLUSIONS: MAAs containing RWE submitted to the FDA were predominantly for rare diseases medicines and for first-in-class indications. Acceptability of RWE varied based on entire body of evidence. Further investigation into factors influencing RWE acceptability and its integration into MAAs across other regulators such as EMA is warranted.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
P62
Topic
Health Policy & Regulatory
Topic Subcategory
Approval & Labeling
Disease
SDC: Oncology, SDC: Rare & Orphan Diseases, STA: Multiple/Other Specialized Treatments