Vertex’s Exa-Cel Off-Target Analyses Set Early Bar For Other Genome Editing Products

US FDA draft guidance does not specify the number of donor samples to test in nonclinical studies or the process for detecting genetic variants potentially susceptible to off-target effects. An advisory committee found adequate Vertex's analyses, which the sponsor called ‘the most comprehensive evaluation of off-target potential performed to date.’

Foggy road
FDA's guidance is foggy on the quantum of evidence needed for nonclinical off-target analyses. • Source: Shutterstock

A lack of specificity in the US Food and Drug Administration’s genome editing draft guidance allowed Vertex Pharmaceuticals Incorporated to set what an advisory committee deemed a sufficiently high bar in its analyses for potential off-target effects with the sickle cell disease gene therapy exagamglogene autotemcel (exa-cel).

Although the FDA’s guidance describes the types of nonclinical studies that are appropriate for analyzing potential off-target edits, it does...

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