Top FDA officials sketched a new regulatory approach designed to expedite bespoke therapies for patients with ultra‑rare conditions. Agency leaders outlined a 'plausible mechanism' pathway that could allow approvals based largely on mechanistic and laboratory evidence coupled with limited clinical data, citing precedent from the custom gene‑editing treatment developed for Baby KJ. The proposals were described in perspective pieces and regulatory commentaries published in leading outlets. The pathway aims to balance speed and evidence in one‑off or very small‑population therapies; reviewers will still need to address manufacturing, reproducibility and post‑approval monitoring. Clarification: 'plausible mechanism' approvals rely on robust biological rationale and surrogate measures when large randomized trials are infeasible.