A Biomarker-Centric Approach to Drug Discovery and Development: Lessons Learned from the Coronavirus Disease 2019 Pandemic

Abstract

Faced with the health and economic consequences of the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the biomedical community came together to identify, diagnose, prevent, and treat the novel disease at breathtaking speeds. The field advanced from a publicly available viral genome to a commercialized globally scalable diagnostic biomarker test in less than 2 months, and first-in-human dosing with vaccines and repurposed antivirals followed shortly thereafter. This unprecedented efficiency was driven by three key factors: 1) international multistakeholder collaborations, 2) widespread data sharing, and 3) flexible regulatory standards tailored to meet the urgency of the situation. Learning from the remarkable success achieved during this public health crisis, we are proposing a biomarker-centric approach throughout the drug development pipeline. Although all therapeutic areas would benefit from end-to-end biomarker science, efforts should be prioritized to areas with the greatest unmet medical needs, including neurodegenerative diseases, chronic lower respiratory diseases, metabolic disorders, and malignant neoplasms. SIGNIFICANCE STATEMENT: Faced with the unprecedented threat of the severe acute respiratory syndrome coronavirus 2 pandemic, the biomedical community collaborated to develop a globally scalable diagnostic biomarker (viral DNA) that catalyzed therapeutic development at breathtaking speeds. Learning from this remarkable efficiency, we propose a multistakeholder biomarker-centric approach to drug development across therapeutic areas with unmet medical needs.

Fig. 1.

Multistakeholder international collaborations enable acceleration of scientific breakthroughs to manage the COVID-19 pandemic. During the COVID-19 pandemic, the biomedical community came together to identify, diagnose, prevent, and treat the novel SARS-CoV-2 virus at breakneck speeds. This was accomplished through international precompetitive multistakeholder collaborations, as illustrated by the color-coded dots to the right of each milestone. Development of a diagnostic biomarker for the viral infection was the catalyst that drove this unprecedented speed, efficiency, and success.

Fig. 2.

End-to-end biomarker strategy to accelerate drug development for unmet medical needs. (A) To maximize the probability of clinical success, a biomarker-centric approach should be adopted during drug development. Biomarkers can be strategically used throughout the drug development pipeline, from initial assessment of target engagement, to safety, efficacy, and finally postmarket approval. Before a novel biomarker can be used to influence regulatory decision-making within a drug development program, it must undergo analytical validation, preclinical or clinical utility studies, and regulatory acceptance. This multistep process closely resembles the phases of the drug development pipeline itself. (B) In an effort to prioritize therapeutic areas that would benefit from a biomarker-centric approach, eight focus areas were identified based on mortality rate, impact on population health, and unmet medical needs. COPD, chronic obstructive pulmonary disease; IBD, inflammatory bowel disease; MDR, multidrug resistant.

Fig. 3.

Collaborative biomarker programs that have accelerated drug development. Driven by multistakeholder teams and consortia, these representative biomarker programs have advanced drug development through implementation of novel biomarkers in pharmaceutical programs and/or qualification of these biomarkers by regulatory authorities. Citations: Petersen et al. (2010); Patterson (2011); Saint-Aubert et al. (2017); Weiner et al. (2017); Mercier et al. (2018); Menetski et al. (2019); Barthélemy et al. (2020). ADNI, Alzheimer’s Disease Neuroimaging Initiative; FNIH, Foundation for the National Institutes of Health; I-SPY 2, investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2; MSG, Mycoses Study Group; PET, positron emission tomography.