Senior FDA officials outlined a new regulatory approach—the so‑called plausible‑mechanism pathway—to accelerate approvals for deeply personalized gene‑editing therapies when randomized trials are infeasible. The perspective, authored by agency leaders and published in a major medical journal, sets principles for demonstrating biological plausibility, safety monitoring, and preclinical evidence for n=1 or ultra‑rare interventions. The guidance builds on the precedent of an individual patient’s gene edit (the “Baby KJ” case) and signals agency willingness to craft flexible evidence standards for individualized medicines. Key elements include robust mechanistic rationale, rigorous quality controls, and post‑approval surveillance commitments. Biotech developers of bespoke gene therapies welcomed clearer expectations but flagged implementation challenges: manufacturing scale, cost, and the need for cross‑institutional frameworks to share learnings while protecting patient safety.