Module 9 2021

19/03/2021

Kymriah: Non-clinical Summary

Lack of non-clinical pharmacology studies was considered acceptable due to the clinical experience with the indication As the product is patient specific it was deemed inappropriate to administer to immune competent animals No adequate animal models to assess the risk of genotoxicity In vitro expansion studies with CAR positive T cells from healthy volunteers and patients showed no evidence for transformation and/or immortalisation of T cells In vivo studies in immunocompromised mice did not show signs of abnormal cell growth of signs of clonal cell expansion for up to 7 months Overall non-clinical package deemed adequate

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The Organisation for Professionals in Regulatory Affairs

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Kymriah: Clinical Results

Four Phase 2, open-label studies investigating the safety and efficacy were conducted Dose was determined based upon dose-response relationship: ● Previous clinical experience: – Efficacy endpoints: response at 3 months, duration of response, time to response, progression free survival, event free survival ● Previous safety concerns: – Occurrence of cytokine release syndrome (CRS); any grade and grade 3/4 – Neurological events – Time to resolution of hematopoietic cytopenia Starting dose determined as 0.6 to 6.0 x 10 8 CAR-positive viable T cells Final dose in SmPC: 1.2 x 10 6 to 6 x 10 8 cells

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The Organisation for Professionals in Regulatory Affairs

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