The Sternfels Prize in Drug Safety Discoveries is an annual award created to foster the reduction of risks associated with the real-world use of pharmaceuticals through recognition of the most novel, clinically relevant and testable idea.
Dr. Miller’s group develops and applies new and powerful strategies to better assess drug liabilities causing significant Adverse Drug Events including cardio- and hepato-toxicity. Insights gained from these studies will generate a strong basis for more informed decision-making in drug development, management and regulation toward safer therapeutic interventions.
Dr. Miller and Allie Schleiff submitted individual proposals on possible projects for the Sternfels Prize.
Dr. Miller proposed determining the mechanistic role of pexidartinib bioactivation in drug-induced liver injury. The adverse outcome is significant enough for black box labeling; however, the FDA still approved the drug last year due to its high efficacy in treating tenosynovial giant cell tumors. The proposed studies would identify the source of that risk for facilitating pharmacovigilance efforts relevant to current clinical use and in the long term, potential insights on ways to engineer out drug liabilities.
Allie Schleiff developed her own proposal from a more generalized perspective reflecting her dissertation research. She integrated bioinformatic, computational, and experimental approaches for rapidly assessing which substituents on a drug scaffold may lead to drug-induced liver injury during metabolism. As a practical test case, she chose to focus on non-steroidal anti-inflammatory drugs (NSAIDs), which are both highly prescribed and frequently hepatotoxic, according to the FDA.