FDA outlines regulatory framework for personalised genome editing therapies

The US Food and Drug Administration (FDA) has outlined a framework that could allow multiple related, patient-specific genome editing therapies to be covered by a single approval, for patients with different genetic variants of the same gene.

The FDA published draft guidance describing how manufacturers could seek approval for closely related individualised genome editing products under a single Biologics License Application (BLA). The aim of these recommendations is to make it more feasible to develop treatments for patients with rare genetic diseases. Due to small numbers of patients with a given genetic variant, clinical trials are often impractical in these conditions.

'This guidance gives sponsors the regulatory clarity they need to develop therapies tailored to each patient's unique genetic makeup, while maintaining the gold standard science that Americans deserve,' said Kyle Diamantas, acting commissioner of food and drugs at the FDA.

The guidance introduces the concept of an 'individualised feature space' (IFS), which defines the variation allowed within the genome editing components of a product while remaining within the scope of a single BLA. This could allow different versions of a therapy to target different pathogenic variants in the same gene. The products would need to use the same mechanism of action and intended editing outcome (eg, correcting a pathogenic variant so that the gene encodes the typical wildtype protein). Other features, such as the formulation and delivery vehicle must also stay the same.

Manufacturers need to show that the genome editing products are safe and effective, supported by data from a clinical trial. However, under the proposed guidance, adding a new product variant within an established IFS would be treated as a manufacturing change, rather than needing a new BLA. Manufacturers would still need to submit a BLA supplement, supported by in vitro evidence demonstrating that the new variant meets the required safety and activity criteria.  

'Families confronting rare genetic diseases deserve more treatment options, no matter how few patients share their diagnosis,' said Robert F Kennedy, Jr, US Department of Health and Human Services secretary.

The draft guidance, which may be revised before being finalised, is open for public comment until 27 November 2026.

The guidance comes as part of wider efforts to accelerate the development of gene therapies and treatments for rare diseases. This includes a recent proposal by the FDA to allow the use of existing scientific and platform knowledge when developing new gene-editing products (see BioNews 1342).