Module 9 2021

Clinical: Benefit / Risk assessment

Integrating γ-retroviral vector may cause leukomogenesis via insertional mutagenesis ● X-SCID GT treated babies developed leukemia in early 2000 ● A more recent case of leukemia observed in ADA patient treated with Strimvelis ● Better understand of vector biology, improved vector design and integration mapping ● New tools for site specific recombination and genome editing 5 deaths occurred in the Juno Rocket trial of cerebral edema in 2016 (last reported Nov. ASH meeting) did not stop CAR-T development Long term severe adverse event might be expected with stem gene therapy A new paradigm is emerging: the hazard is part of the MoA and of the potential benefit

Novartis Pharma AG- Business use only- not for further distribution

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