Pharmacodynamic Biomarkers: Accelerating Biosimilar Development for Cost-Efficiency and Public Health Impact

Developing and approving biosimilars is crucial for improving patient access to safe, effective, and affordable treatments. According to a study published in Clinical Pharmacology & Therapeutics, the US Food and Drug Administration (FDA) is exploring pharmacodynamic (PD) biomarkers as an alternative to costly and time-consuming comparative clinical studies to enhance the efficiency of biosimilar development and approvals.

The FDA is investigating the use of PD biomarkers to streamline biosimilar development. The FDA recommends thorough comparative analytical assessments, including structural and functional characterization, animal data, and human pharmacokinetic (PK) and PD studies, to demonstrate biosimilarity. PD biomarkers, which measure a biological response to a drug, can offer a more sensitive and cost-effective approach than traditional clinical studies. While PD biomarkers have not been widely used in biosimilar approvals, there is growing potential to incorporate them into development programs, reducing the reliance on comparative clinical studies with efficacy endpoints.

As of June 2022, only 11 of 36 approved biosimilars included PD similarity data. These biosimilars, covering products like filgrastim, pegfilgrastim, insulin glargine, and epoetin, utilized well-characterized PD biomarkers such as absolute neutrophil count, CD34+ cells, reticulocyte count, and hemoglobin level. Including PD biomarkers in biosimilar development can lead to shorter, less costly clinical studies, often conducted in healthy participants.

The FDA emphasizes that the purpose of a biosimilar development program is to demonstrate similarity to the reference product, not to establish safety and effectiveness independently. The FDA's Biosimilars Action Plan, initiated in 2018, aims to advance the science around PD biomarkers for biosimilars, providing information resources and development tools to assist sponsors in developing high-quality products.

Clinical pharmacology studies conducted by the FDA, including 3 studies with 2 originator biologics each, contribute valuable data on PD biomarkers, dose-response relationships, and model-based approaches. These studies exceed typical pilot study designs to ensure robust information is available for evaluating different analysis methods and identifying novel biomarkers. The FDA's ongoing efforts aim to clarify expectations for using PD biomarkers in biosimilar development, enhancing the regulatory framework.

"Utilization of PD biomarkers can help streamline biosimilar development programs as the current process can be costly and time‐consuming," said coauthors.

While PD biomarkers have not been extensively used in biosimilar approvals to date, ongoing research, and the FDA's initiatives provide a foundation for leveraging these biomarkers to support biosimilarity, ultimately benefitting public health by accelerating the introduction of additional treatment options.

Reference

Strauss DG, Wang YM, Florian J, Zineh I. Pharmacodynamic biomarkers evidentiary considerations for biosimilar development and approval. Clin Pharmacol Ther. 2023;113(1):55-61. doi:10.1002/cpt.2761