Biomarkers in drug development: a double-edged sword?

Mariya Gromova and Aleksandra Nevmerzhitskaya

by Mariya Gromova and Aleksandra Nevmerzhitskaya

As of April 2020, more than 33 000 clinical trials involving biomarkers were registered according to the database, including around 4000 Phase 3 and 4 trials. Figure 1 shows the number of drugs approved by EMA and FDA with at least 1 biomarker used during development (biomarker acceptance) between 2015 and 2019. It can be clearly seen that more than half of the approvals were supported by biomarker data during at least 1 of the development stages. The proportion of approvals with biomarkers is comparable between EMA and FDA with average of 69% and 59%, respectively. There has been a slight increase in acceptance of biomarkers in recent years, even though the growth is not continuous.

Figure 1: EMA and FDA drug approvals with and without biomarkers between 2015 and 2019


Figure 1: EMA and FDA drug approvals with and without biomarkers between 2015 and 2019

Biomarker acceptance varies significantly with the pharmacotherapeutic group of the drug. As illustrated in Figure 2, for certain pharmacotherapeutic groups, approvals with biomarkers are more common than without. Examples include immunosuppressants, immunostimulants, drugs used in diabetes, antithrombotic drugs, antineoplastic agents and antivirals.

Figure 2: Selected EMA drug approvals with and without biomarkers between 2015 and 2019 by pharmacotherapeutic group


Figure 2: Selected EMA drug approvals with and without biomarkers between 2015 and 2019 by pharmacotherapeutic group

One of the main challenges in the biomarker field is to distinguish between a potential biomarker and a reliable biomarker that can be universally used to guide important clinical and commercial decisions. As a response to the increasing need to address quality and suitability of biomarkers, concepts of biomarker qualification and validation have been developed. Biomarker validation refers to the validation of analytical assays, that is, assessment of performance characteristics, such as, for example, precision, accuracy, detection limit and robustness. Biomarkers qualification, on the other hand, is providing evidence that biomarker is linked with a certain biological process and clinical endpoint.

Even though biomarker development and qualification is usually resource- and time-intensive, it is not surprising that a considerable number of approvals is affiliated with biomarkers, as this goes along with a number of benefits for both patients and drug developers:

  • Biomarkers support selection of the most favourable drug candidates, significantly reducing discovery costs and probability of failure at later stages.

  • Biomarkers facilitate regulatory and development decisions.

  • Precise patient stratification and reduced number of patients needed to show clinical benefit and non-inferiority in clinical trials are potentiated by biomarkers use.

  • Biomarkers may be used as surrogate endpoints for a clinical study. From drugs approved by FDA in March-May 2016, 27% have used at least 1 surrogate marker as a primary endpoint. For example, Odefsey (treatment of HIV-1 infection) was approved based on 2 surrogate markers: Viral suppression and CD4+ cell counts (2).

  • From the approval perspective, biomarkers are helpful to determine the benefit-risk profile for a drug under development, thus, allowing a more straightforward decision making by regulatory agencies.

Overall, the use of biomarkers in a suitable way has a potential to make development more sustainable, improve the quality and safety of a drug, reduce development costs and accelerate approval processes significantly. If you want to get more information about the current global regulatory landscape for biomarkers, including companion diagnostics, and understand how biomarkers can add substantial value to your development programme, read the comprehensive review article published by the Biopharma Excellence team in Biomarker Insights (1).

Biopharma Excellence is offering a customized strategic approach to overcome challenges linked to biomarkers development, allowing to maximize the benefits of biomarkers for the accelerated development and approval of your product. Interested in learning more about how your biomarker development program can be optimized in agreement with expectations of regulatory agencies? Get in contact with us.


  1. Gromova M, Vaggelas A, Dallmann G, Seimetz D. Biomarkers: Opportunities and Challenges for Drug Development in the Current Regulatory Landscape. Biomarker Insights. December 2020. doi:10.1177/1177271920974652

  2. Baker DE. Surrogate markers and drug approvals. Hosp Pharm. 2016;51:611-614.

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