P223: Characterization of Drugs with REMS Elements to Assure Safe Use (ETASU)
Poster Presenter
Meha Ahmed
ORISE Research Fellow
U.S. Food and Drug Administration United States
Objectives
For drugs with serious safety risks, implementing Elements to Assure Safe Use (ETASU) may be required prior to marketing a drug as part of a Risk Evaluation and Mitigation Strategy (REMS). We described the relationship among ETASU, therapeutic category, and risks the REMS are intended to mitigate.
Method
We examined the required ETASU A (provider certification), B (dispenser certification), C (administered at certain settings), D (safe-use conditions such as lab work), E (monitoring), and F (patient registry), with the associated REMS risks and the drug therapeutic categories.
Results
A REMS is a drug safety program that specifies the required ETASU A-F for certain medications with serious safety concerns to help ensure safe drug use. Using publicly available REMS materials, we identified drugs with an active ETASU then tabulated the ETASU and risk information. We grouped the drugs into therapeutic categories.
As of October 7, 2024, we identified 68 drugs with an active ETASU. Sixty-three of the 68 drugs (93%) included ETASU B, followed by ETASU A (52, 76%), and D (42, 62%). Less than 25% of the drugs had ETASU C (13, 19%), ETASU E (16, 24%), or ETASU F (15, 22%). Embryo-fetal toxicity (n=16 drugs) and serious infections (n=11 drugs) were the most common risks, followed by cytokine release syndrome and neurologic toxicities (n=7 drugs), heart disease (n=6 drugs), overdose/abuse (n=5 drugs), hepatotoxicity (n=4 drugs), respiratory distress (n=4 drugs), sedation (n=3 drugs), anaphylaxis (n=3 drugs), and death (n=2 drugs). The remaining 7 risks (suicidal behavior, glomerulonephritis, neutropenia, hypotension, neoplasm, osteosarcoma, and vision loss) were each associated with a single drug.
Seven of the 68 drugs with life-threatening risks (e.g., anaphylaxis) required three or more elements. We identified one REMS that included all six elements. ETASU A, B, and D were frequently used for the risk of embryo-fetal toxicity, serious infections, hepatotoxicity, overdose/abuse, or suicidal behavior. Additionally, these three ETASU are often used to manage the risks associated with therapeutic categories such as complement inhibitors (e.g., serious infections) and endothelin receptor antagonists (e.g., hepatoxicity, embryo-fetal toxicity). Notably, CAR T-cell therapies require ETASU B and ETASU C while bispecific B-cell engagers require ETASU A and B. The different requirements likely reflect distinct administration methods (intravenous infusion vs. subcutaneous injection) and the risk profile.
Conclusion
Irrespective of the risk or therapeutic categories, our findings show REMS programs most commonly require training and special certification followed by documentation of safe use conditions such as blood testing. However, notable patterns were observed among several risk categories, suggesting that ETASU requirements are tailored to specific risks, with more complex or severe risks generally requiring comprehensive ETASU. Other drug characteristics such as route of administration may also influence the requirements, thus further investigation may provide additional insight.
