The US Food and Drug Administration (FDA) has unveiled a new regulatory framework designed to accelerate the approval of personalised therapies by easing traditional requirements. The initiative, termed the “plausible mechanism pathway,” was inspired by the landmark case of Baby KJ, whose life-saving gene-editing treatment became the model for this approach.
Baby KJ, a newborn diagnosed with carbamoyl-phosphate synthetase 1 (CPS1) deficiency, a rare and severe metabolic disorder, was treated under a single-patient, expanded-access investigational new drug (IND) application that the FDA processed within a week. The patient’s medical team developed a customised CRISPR-based therapy to repair the underlying gene defect. In May 2025, KJ became the first individual worldwide to receive a bespoke CRISPR treatment, marking a milestone that would later shape the new regulatory pathway.
Under the new framework, the FDA will consider therapies targeting well-defined molecular or cellular abnormalities rather than broadly characterised diseases. To qualify, the treatment must act on the biological source of the disorder and address a condition with a clearly documented natural history. Evidence of successful gene or molecular targeting through animal or non-animal models, or biopsy where relevant, will be required. Moreover, the product must show measurable improvement in patient outcomes, with the agency applying a lower threshold for diseases that cause progressive decline. Notably, the plausible mechanism pathway eliminates the need for traditional clinical trial data, relying instead on expanded-access programmes to gather real-world safety and efficacy information.
The FDA will grant marketing authorisation once developers demonstrate consistent success across several patients, continuing to monitor long-term results through real-world evidence (RWE). While the scheme prioritises rare disorders, it could extend to more common conditions lacking proven treatments.
The move aligns with the Trump administration’s efforts to expand access to personalised therapies and reduce long-term treatment costs.
