Bridging the Gap in Drug Development: Using QSP to Realize Phase 2 Success
Author: Sarah Yunes
Editors: Jae Yang and Rajiv P. Shrestha
Dr. Gianluca Nucci presenting to Boston QSP audience.
To quantify risks and benefits of drug products in development, model-informed drug development (MIDD) combines trial performance, PK/PD of disease models, decision criteria, information on competing drugs, and models of data analysis & trial design.
MIDD has been successfully applied at Pfizer to increase efficiency and objectivity in trial design and development decisions. Although MIDD has impacted Phase 3 success rate, it has not brought substantial improvements to Phase 2 success yet. The majority of failures result from insufficient efficacy to differentiate from the standard of care. How best could we address this problem using quantitative systems pharmacology (QSP)? Our March speaker, Dr. Gianluca Nucci. Dr. Nucci, Head of Early Clinical Development Clinical Pharmacology at Pfizer, presented Quantitative Pharmacology: A Pillar for Translational Research.
Several factors contribute to improving Phase 2 success and thus increasing the number of drugs that successfully treat patients on the market. Among them, key factors include getting the right molecule, testing it on the right patients and disease, getting the correct dose, and confidence in the target selection. To be confident that the molecule being targeted is going to test the mechanism, the molecule should satisfy the Three Pillar of Survival: the drug needs to get to the target, the drug needs to bind the target, and the drug needs to effect change in the pharmacological activity. MIDD has been very helpful in determining the correct molecule and dosing for the patients, but despite this, the rate of Phase 2 success has not markedly improved.
This is where QSP can be the most effective. To increase the confidence in target translation, there needs to be a deep understanding of the pathway involved in the disease and how modulating this pathway could change the disease state. QSP models capture the complexity of human biology as it relates to both pharmacology and disease. During the talk, different nonclinical and clinical case studies were presented to highlight the importance of using QSP to connect what is known about a drug target and disease biology to predict how modulating the target can lead to disease treatment.
Dr. Gianluca Nucci (left) and Boston QSP Scientific Writer Sarah Yunes (right) during the interview
Since Dr. Nucci began his career, QSP has progressed from something that was relatively rare to a rapidly growing field, aided by improvements both in disease understanding and in technology that increased modeling speed. Dr. Nucci called QSP “an emerging discipline” with increasing impact through the industry, but it still hasn’t broken through to become “business as usual”. To fully realize the potential QSP provides, it must be more widespread and better integrated into the standard MIDD tools. As a Scientific Advisor for Boston QSP, Dr. Nucci spoke highly of the Boston QSP organization, saying Boston QSP is successful because “it connects the community with a vision that’s broad, encompassing big and small pharma, consultancy, academia and embracing the diversity we have in town”. When he’s not working on drug development, Dr. Nucci enjoys spending time being active outdoors with his family. Some of his favorite activities include running, biking, swimming, snorkeling and skiing.
Dr. Nucci’s talk was followed by a mixer event where community members discussed and socialized over food and drinks. Check out the March Event: The Photo Blog for more details and highlights.
Dr. Nucci told us that he had the pleasure of presenting at the Boston QSP March event. Upon request, Dr. Nucci shared the presentation blew.
We would like to thank Pfizer for sponsoring the event and the Cambridge Innovation Center (CIC) for sponsoring the venue.
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