Demonstrating Efficacy When Clinical Trials Are Impossible: QSP Modeling to
Support a 505(b)(2) Application
Rebecca Baillie, PhD, Christina Friedrich, PhD, Jake Nichols, PharmD, MBA
Principal Scientist, Chief Engineer, Rosa & Co. San Carlos, CA; Director of
Medical Affairs, US WorldMeds, Louisville, KY
Wednesday, April 19, 2023, 9:00 to 10:00 am PDT
Register at https://rosaandco.com/webinars
Abstract:
For over 50 years, fentanyl has been used in anesthesia and pain control, with
naloxone as a counter agent to reverse overdoses. The increasing abuse of
synthetic opioids has necessitated expanding the use of naloxone from hospitals
and clinics to community use. The need for increased naloxone dosing, speed of
onset, and ease of use has led to the development of intramuscular (IM) dosing
devices for community use. Because overdose clinical trials are problematic to
implement and require consent after the opioid has been administered, the FDA
has recommended modeling of opioid receptor displacement of potent opioids with
naloxone as an alternative method to guide dose recommendations.
This webinar discusses the development of a mu-opioid receptor binding
quantitative systems pharmacology (QSP) model with competing drug treatments
(naloxone, fentanyl). The model was used to support regulatory approval of a
higher clinical dose of naloxone in an IM device to address the unmet medical
need. Simulations using the model demonstrated the added utility of higher
naloxone doses in displacing fentanyl from the mu receptor. QSP modeling
demonstrated that higher doses of naloxone lead to a greater displacement of
fentanyl from the mu receptor and reduce the time it takes for fentanyl binding
to dip below a critical threshold for overdose reversal. The modeling increased
confidence in the added utility of the higher-dose naloxone product and
supported approval by the FDA.