FDA’s Proposed Gene‑Therapy Pathway Could Accelerate Bespoke Treatments — Key Questions Remain

The US Food and Drug Administration has outlined a proposed pathway that could speed access to highly personalised gene therapies for patients with clearly defined molecular defects. The proposal, described in a paper by FDA commissioner Martin Makary and CBER director Vinay Prasad, draws on the rapid approval route used in the case of Baby KJ, whose customised CRISPR treatment was authorised through an expanded‑access IND and delivered in May 2025.

The pathway is intended for interventions that target a specific molecular or cellular abnormality and directly address the biological cause of disease. Under these conditions, sponsors might be able to proceed to clinical use without a traditional clinical trial, provided the FDA receives appropriate preclinical safety data before patient dosing.

What the Baby KJ case shows

Baby KJ, a newborn with a severe carbamoyl‑phosphate synthetase 1 (CPS1) deficiency, received a bespoke CRISPR gene‑editing therapy after the FDA processed a single‑patient, expanded‑access investigational new drug (IND) application in one week. The case demonstrates how regulators can move quickly when there is a clear molecular target and urgent clinical need.

Outstanding questions and industry concerns

Terry Pirovolakis, CEO of Elpida Therapeutics — a company that specialises in acquiring discontinued gene‑therapy programmes — welcomed the potential of the pathway but stressed that important details remain unresolved. Key issues include which vector components and platform variations the FDA will accept under this approach, and whether the pathway can apply beyond single‑patient cases to small patient cohorts.

Terry Pirovolakis (TP): "It wasn’t formal guidance — it was published as a paper — but it gives us a useful reference when preparing filings for rare‑disease programmes. Ultra‑rare conditions that affect as few as one to 5,000 patients deserve their own route."

TP noted that reuse of identical elements — such as promoters, capsids or transgenes — is often impractical across different diseases. He said the pathway would be far more impactful if regulators accept some variation in components (for example, different capsids or promoters) rather than requiring exact matches.

Another concern is commercial viability. Pirovolakis argued many programmes are discontinued not because they cannot reach the clinic, but because the route to commercialisation and incentives such as the priority review voucher (PRV) have become uncertain. The current proposal may ease clinical access, he said, but does not restore commercial incentives that encourage continued investment and scale‑up.

Broader implications

If implemented with sufficient breadth, the pathway could enable more rapid development of personalised gene‑editing, gene‑replacement and antisense oligonucleotide (ASO) therapies. A larger base of approved therapies would likely reduce manufacturing costs and reshape industry dynamics, but that outcome will require clearer regulatory boundaries and renewed commercial support.

Bottom line: The FDA’s proposal marks an important step toward faster personalised gene therapies, but clarity is needed on eligible platforms, component variability (capsids, promoters, transgenes) and economic incentives before the approach can scale beyond isolated cases.

Source: Paper by Martin Makary and Vinay Prasad; interview with Terry Pirovolakis.