Module 9 2021

22/03/2021

IMMUNOGENCITY

• Immunogenicity usually secondary endpoint • Sometimes FDA will require a formal immunogenicity study • “a one-sided design will ordinarily be

adequate to compare clinical immunogenicity of the proposed product and reference product.” • Setting margin can be challenging as one cannot rely on historical data – need to consider adaptive trials

Kozlowski et. al. “the FDA will evaluate immunogenicity in a risk-based manner.”

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IMMUNOGENICITY DATA GAINING IMPORTANCE

In some circumstances in US and EU immunogenicity is being requested as primary endpoint in patient studies particularly for hormones where efficacy can be established in healthy subjects. Immunogenicity studies are challenging Robustness of assay – Coherus PegFilgrastim: FDA rejected BLA requesting a ‘re- analysis of a subset of subject samples with a revised immunogenicity assay’ 1) ● Size of study: 100 – 600 patients: Coherus recruited 300 healthy subjects – Driven by incidence – Impact on efficacy safety

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