January 17, 2024
Molecular imaging in clinical trials to reduce costs of failure
For many years pharmaceutical companies have been struggling with high failure rates. Around 90% of clinical drug development fails, costing the industry billions. While the process of bringing a new drug to market is divided into fixed, required steps, the study design may differ. This is where there are opportunities to increase the chances of success and reduce costs.
About this article
This article discusses two trends in drug development. One of them is the use of molecular imaging to gather extra data from the same clinical trial phases that drug developers are used to. The other is implementing Phase 0 with molecular imaging as a first-in-human trial to save time and costs and to increase chances in subsequent trials. This article is written together with TRACER CRO, a contract research organization specializing in imaging, and experienced in the Phase 0 clinical trial.
Incorporating visualizing CD8 T-cells and Phase 0 clinical trial in your drug development process
CD8 ImmunoPET™ imaging allows the study of the immune response through downstream signaling. ImaginAb’s CD8 ImmunoPET™ agent is a developed a radiolabeled minibody that specifically targets the CD8 receptor, enabling the in vivo mapping of CD8+cells throughout the human body to visualize the immune response status. This minibody can be used in a diagnostic and theranostic setting, resulting in a physical profile of a patient's immune status and to measure response to treatment. The same method can be used in drug development to visualize the effect of a new drug by CD8 ImmunoPET™ Imaging. This can also be used in Phase 0 for early PK/PD data of the compound in patients.
Imaging of immune response in clinical trials
Good to know: Multiple imaging processes can be done simultaneously in a clinical trial. A compound can be labeled with a radionuclide to image the on- and off-target behavior of the compound itself. CD8 ImmunoPET™ imaging provides information on downstream signaling and immune status. Making it especially beneficial for many therapeutic drugs, vaccines and/or cell therapies that can modulate the immune response throughout the body and/or in tumours. Contact ImaginAb to discuss the possibilities of CD8 ImmunoPET™ Imaging.
Prevent false negatives by enhanced personalized medicine patient stratification
That a drug does not work on one specific patient or single tumor does not mean that the drug is ineffective. Molecular imaging can provide proof of, or change in target expression in individual patients and each specific tumor and lesion. This allows drug developers to understand whether drugs have different efficacies dependent on location or type of tumor lesion or type of cancer being treated, allowing them to make better decisions regarding how the move forward with the clinical development of new drug candidates. This is all data that can be gathered by adding molecular imaging to a clinical trial.
Start clinical trials with GLP material
To avoid costs in the early phases of drug development, drug developers can start their clinical trials from GLP material. For in-human use of a compound, GMP is always mandatory, but when the GLP material is labeled under GMP conditions, the end product is GMP grade. In a Phase 0 study with imaging, the labeled compound can be used. For the Phase 1 study, an unlabeled compound is commonly needed. Phase 0 is an addition to the regular drug development process but can, depending on the context, replace large animal models in the preclinical trajectory. This allows drug developers to go in-human faster and avoid strict regulation. An extended single-dose toxicity study is often not required since Phase 0 uses a microdose of the compound.
Phase 0 as an alternative for large animal models
To test a drug in large animal models, regulations can be tough while the value of the acquired data from those experiments can be difficult to extrapolate to humans. Phase 0 allows drug developers to test their drug early in-patient and can allow them to skip extensive testing in large animal models before Phase 0. This means time and costs can be reduced, while the relevance of the data can increase. Both the FDA and EMA support Phase 0 studies, hoping it will bring down the failure rate of new compounds.
Reduce costs of failure in drug development
Terminating research at an early stage for drugs that will ultimately fail, can reduce clinical costs significantly. By reducing phase lengths, capitalized total cost can be reduced further. For example, if phase lengths could be reduced by 25%, capitalization costs per approved drug could drop by 16%.
Probability of Technical and Regulatory Success (PTRS)
Innovating clinical trials, and especially Phase 0 can play a crucial role for a pharmaceutical company to improve the Probability of Technical and Regulatory Success (PTRS). It allows the identification of promising compounds and portfolio progressions. Other levers that leverage the PTRS are digital biology, AI-driven predictive approaches, regulatory innovation, and new science.
Increase chance of success in clinical trials
Data obtained from imaging during Phase 0 can allow drug developers to optimize subsequent clinical trials. Here are some of the important factors of clinical study design that it can impact: drug target, inclusion criteria, endpoint definition, treatment response assessment, safety monitoring, sample size determination, and biomarker validation.
Early phase clinical trials: Phase 0 vs Phase 1
In conclusion, we compare the well-known Phase 1 study with the innovative Phase 0 study. Both are early-phase clinical trials and both can be the first-in-human study. The biggest difference is the study objective. Phase 1 is about optimal dose-finding, often in healthy volunteers and without measuring efficacy. Phase 0 on the other hand uses a microdose and therefore does not provide information on the optimal therapeutic dose. Imaging can show if the target of interest is reached, if binding occurs, where off-target accumulation exists, and what the method of excretion is.
What is the right clinical trial design for you?
Are you a drug developer on the path to your clinical trial? Or are you an investor, or medical professional, or are you in a different role in the field of drug development? We would like to get in contact so we can advise on what clinical trial design suits your compound and objectives. For information about CD8 ImmunoPET™, contact ImaginAb. For more information on clinical trials – like Phase 0, contact TRACER at https://www.tracercro.com/.