The rapid evolution of gene therapies and gene editing modalities in particular is challenging how personalised medicines are developed and evaluated. Many rare genetic disorders consist of numerous disease-causing variants, each of which requires a distinct therapeutic intervention. While advances in gene editing are making such treatments increasingly feasible, conventional development pathways are difficult to apply when patient populations are extremely small and individual mutations may be encountered only rarely. Requiring a complete development package, toxicology programme and clinical evidence package for every variant-specific therapy would make novel treatments impractical to develop.
In recognition of this challenge, the US Food & Drug Administration (FDA) issued a draft guidance in February 2026 describing a plausible mechanism framework for individualised therapies targeting specific genetic conditions with known biological cause (docket: FDA-2026-D-1256).1 Rather than treating every variant-specific therapy as an entirely new product, the framework explores how evidence may be generated and leveraged across therapies that share a common biological cause.
The framework relies on several components: identification of a known causal genetic or molecular lesion; an understanding of untreated disease progression; evidence that the therapy engages with its intended target; and finally, demonstration that clinical outcomes reflect correction of the underlying genetic defect. With this approach, the FDA framework acknowledges that personalised therapies may be developed in settings where the first-in-human study also contributes pivotal evidence supporting effectiveness.
