Pharmacodynamic Biomarkers for Biosimilar Development and Approval: A Workshop Summary.

The US Food and Drug Administration (FDA) Biosimilars Guidance describes how biosimilars may be approved based on clinical pharmacokinetic and pharmacodynamic (PD) biomarker data, without comparative clinical studies with efficacy end points. This type of clinical development program, however, has only been implemented for a small number of FDA-approved biosimilar products over the last decade. To encourage the use of PD biomarkers in biosimilar development and approval, the Duke-Margolis Center for Health Policy collaborated with the FDA to host a two-day virtual public workshop entitled "Pharmacodynamic Biomarkers for Biosimilar Development and Approval" on September 20-21, 2021.

Considerations for Use of Pharmacodynamic Biomarkers to Support Biosimilar Development - (III) A Randomized Trial with Interferon Beta-1a Products.

The US Food and Drug Administration (FDA) has taken steps to bring efficiency to the development of biosimilars, including establishing guidance for the use of pharmacokinetic and pharmacodynamic (PD) similarity study data without a comparative clinical study with efficacy end point(s). To better understand the potential role for PD biomarkers in biosimilar development and inform best practices for biomarker selection and analysis, we conducted a randomized, double-blinded, placebo-controlled, single-dose, parallel-arm clinical study in healthy participants. Eighty-four healthy participants (n = 12 per dose arm) received either placebo or one of three doses of either interferon β-1a (7.

Considerations for Use of Pharmacodynamic Biomarkers to Support Biosimilar Development - (I) A Randomized Trial with PCSK9 Inhibitors.

US Food and Drug Administration (FDA) guidance outlines how biosimilars can be developed based on pharmacokinetic (PK) and pharmacodynamic (PD) similarity study data in lieu of a comparative clinical efficacy study. There is a paucity of PD comparability studies in biosimilar development, leaving open questions about how best to plan these studies. To that end, we conducted a randomized, double-blinded, placebo-controlled, single-dose, parallel-arm clinical study in healthy participants to evaluate approaches to address information gaps, inform analysis best practices, and apply emerging technologies in biomarker characterization.

Considerations for Use of Pharmacodynamic Biomarkers to Support Biosimilar Development - (II) A Randomized Trial with IL-5 Antagonists.

The US Food and Drug Administration (FDA) guidance describes how pharmacodynamic (PD) biomarkers can be used to address residual uncertainty and demonstrate no clinically meaningful differences between a proposed biosimilar and its reference product without relying on clinical efficacy end point(s). Pilot studies and modeling can inform dosing for such PD studies. To that end, we conducted a randomized, double-blinded, placebo-controlled, single-dose, parallel-arm clinical study in healthy participants to evaluate approaches to address information gaps, inform best practices for analysis of biomarker samples and study results, and apply emerging technologies in biomarker characterization.