By Elisabeth Rouits, PharmD, PhD, Global Head Clinical Pharmacology-Pharmacometrics
This article is part of a multi-part series on the opportunities and complexities in developing targeted medicines and bringing them to market.
In developing targeted medicines, organizations must consider a comprehensive pharmacological approach. This is essential for optimization of drug dosing1 and administration based on individual patient characteristics, metabolic capacities, and genetic influences. By customizing treatment regimens, organizations can maximize efficacy, minimize side effects, enhance treatment response, adapt to patient needs over time, and navigate regulatory requirements more effectively.
- Points to consider
- Identify and quantify patient‑specific characteristics that influence drug metabolism, response, and safety.
- Adopt an iterative approach to continually refine dosing strategies throughout clinical development, taking into account evolving patient needs, disease characteristics, and treatment responses.
- Plan on generating comprehensive pharmacokinetic and pharmacodynamic data to support dosing regimens and meet regulatory requirements.
- Understand the value of translational medicine and dosing‑optimization efforts.
- Maximizing efficacy: Individuals vary in their responses to targeted medications due to differences in individual metabolisms, genetic makeups, and other factors.2 By understanding those individual characteristics, companies can tailor drug doses to maximize drugs’ efficacy. For example, some patients may metabolize drugs more quickly — or more slowly — than others, requiring adjustments in dosage to achieve optimal therapeutic levels.
- Minimizing side effects: Drug toxicity and adverse reactions can occur when drug exposures are too high for a particular individual or when a patient’s metabolism processes drugs differently. By customizing dosing regimens, dose level and dosing frequency, healthcare providers can minimize the risk of side effects and enhance patient safety. Such a personalized approach reduces the likelihood of patients’ experiencing adverse reactions and improves patients’ overall treatment experience as well as compliance.
- Enhancing treatment response: Targeted medicines often rely on specific molecular pathways to exert their therapeutic effects. When treating a cancer patient with a targeted medicine, by considering individual genetic influences and the tumor characteristics of target density, target occupancy, target genetics, target engagement, and target accessibility, healthcare providers can tailor treatment to target those pathways more effectively. A personalized approach increases the likelihood of positive treatment response and may lead to better long-term outcomes for patients.3
- Adapting to patient needs over time: Needs may change during the course of treatment due to disease progression, changes in metabolic functions, or resistance to medications. A comprehensive approach to targeted medicines involves continual monitoring and adjustment of dosing strategies throughout the clinical development process. That iterative process ensures treatment remains optimized to meet individual patients’ evolving needs and to maximize the chances of treatment success.
- Navigating regulatory requirements: Regulatory authorities increasingly require pharmaceutical companies to justify dosing regimens based on comprehensive pharmacokinetic and pharmacodynamic data that characterize exposure–response relationships.4 A personalized approach to drug dosing and administration requires rigorous scientific evidence to support a drug’s efficacy and safety. By incorporating translational medicine expertise into clinical development, companies can navigate regulatory requirements more effectively and streamline the approval process for targeted medicines.
Bridging the gap between preclinical research and clinical development
Companies need to know how drug disposition and pharmacological effects observed in preclinical studies as well as in vitro characteristics translate into human patients. That process is fundamental to the design of effective dosing regimens for clinical trials and eventual patient treatment. Groundbreaking patient-specific preclinical models such as induced pluripotent stem cells and organoids have revolutionized targeted-therapy development by providing clinically relevant information early and thereby accelerating the transition to the clinical development phase.5
By applying translational medicine principles, such as model-informed or quantitative pharmacology approaches, companies can identify and quantify patient‑specific factors that influence drug metabolism, response, and safety. Such personalized dosing strategies will optimize treatment outcomes while minimizing adverse effects.
Translational medicine is an iterative process that spans the entire clinical development pathway and requires continual refinement of dosing strategies based on evolving patient needs, disease characteristics, and treatment responses. An iterative approach ensures that treatment remains optimized and effective throughout the course of clinical trials and beyond.
Translational medicine expertise is essential for generating the evidence needed to navigate regulatory hurdles and obtain approval for targeted therapies.
1 https://academic.oup.com/jnci/article/115/5/492/6935793
2 https://academic.oup.com/jnci/article/115/5/492/6935793
3 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10895472/
4 https://academic.oup.com/jpp/article-abstract/71/4/699/6122189
