Using Biomarkers For Clinical Development and Regulatory Approval
Our February group came together for an hour of specialist discussion about the current state of Biomarker utility during clinical development and future directions of regulatory approval. This discussion group was a select group of approximately 15-20 key industry leaders from various pharmaceutical and biotech companies. Deepti Aurora-Garg, Executive Director Companion Diagnostics, at Merck, moderated the discussion, and notable attendees included senior representatives from Sanofi, Takeda, PsiOxus Therapeutics, Novartis, Abbvie, World Health Organization, and many more.
Aurora-Garg kicked off the discussion with a brief overview of the utility of biomarkers in developing clinical trials and design and the regulatory considerations associated with it. During this, Aurora-Garg alluded to how the current landscape has been affected by COVID-19.
“Because of COVID, we are seeing budgets being cut, which means there will be a lot of reliance on designing trials that are more tailored and have a higher probability of success, over the coming years” she explained. “Consequently, it is going to be a smart move for nearly every pharmacological and biotechnology point of view to venture further into the biomarker space”, Aurora-Garg continued. The best way to design smarter trials moving forward is to adopt the modified approach of biomarker assessment. Incorporating clinical biomarkers into the design process also encourages and increases the chances of regulatory approval.
Regulatory approval beyond continental regulatory agency is paramount for a drug candidate or device to reach maximum impact.
The overview continued with discussion of the best practices associated with gaining regulatory approval. In particular, Aurora-Garg explained, “where the field has evolved, as from, my own experience, it is advisable to start with regulatory approval in the US and then go global”. This is because “every regulatory agency treats the use of biomarkers differently, especially if you are coming from a stratification or enrichment point of view”. Regulatory approval beyond continental regulatory agency is paramount for a drug candidate or device to reach maximum impact. Global registration is preferable, meaning there is an undeniable industry emphasis on incorporating biomarker analysis and validation into meaningful clinical decisions.
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Once the introduction concluded, the debate began. One audience member opened the floor with the question of how best to register biomarkers. Viable frameworks for first-time identification of biomarker design are essential to ensure this. As Aurora-Garg pointed out, “it’s of no use for the pharmaceutical industry to take steps to integrate biomarkers into clinical trials unless we can execute it properly”. For a biomarker to work, it must become a companion diagnostic or a complementary diagnostic that is able to sustain the manufacturing process. The audience member in question queried the best practice for developing companion diagnostics and whether there is an advantage of using either one over the other. Advice offered included looking for the prevalence of the biomarkers and assessing the wider applicability of the biomarker test, which would then determine the appropriate diagnostics.
The panel continued with discussion of the difficulties of bridging for target therapy and patient selection. As one audience participant shared how, “doing a bridging study between a local assay, which may or may not be as qualified as a trained lab for a companion diagnostic, may not have the same antibodies”. The said party continued, “bridging this to something that requires further development with a different test is equivalent to poking yourself in the eye with a sharp stick; it is a very difficult thing to do”. For instance, it will be challenging to determine the appropriate target population, which depends entirely on the analytical character of the test, as well as the clinical linkage to the analytics. Bridging can significantly impact cost, with other audience members agreeing that “conducting up-front local testing will inevitably delay proceeding by up to a year or even 18 months whilst clinicians develop the appropriate companion diagnostics”.
Global registration is preferable, meaning there is an undeniable industry emphasis on incorporating biomarker analysis and validation into meaningful clinical decisions.
Aurora-Garg also highlighted how “typically the FDA doesn’t want to see more than 20% unavailable samples from a clinical trial, you need as least 80% available samples evidenced”. This means that sample availability for bridging is not always achievable unless clinicians breach the intent to collect samples, which will be stable enough to be tested with the final device. Regulatory bodies require extensive details and a local test provided in candidate submission. Therefore, it is advisable to collect all information possible with the local test results, irrespective of how heterogeneous it may be. A preferred path is to not use local testing, which according to Aurora-Garg, “enables a better degree of testing control”.
The discussion group concluded with some final thoughts on the future of technologies such as genome and single-cell RNA sequencing for clinical development. With ongoing research and development and numerous exciting platforms emerging in the field, the future looks bright for the biomarkers field. At Oxford Global, we couldn’t have been more pleased with the turnout for our February biomarkers discussion group. The conversation was engaging, the debate stimulating, and the industry insights invaluable. We will continue our discussion group series in March with a session focusing on Translational Biomarkers To Guide Clinical Development For Allogenic CAR T Cell Therapies. Learn more about the Oxford Global discussion group series at our Biomarkers Portal.
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