Potentially revolutionary FDA gene therapy pathway leaves key issues unresolved

The US Food and Drug Administration (FDA) has introduced a potential game-changing pathway for gene therapies, though its exact boundaries are still uncertain. An article in the New England Journal of Medicine, co-authored by FDA Commissioner Martin Makary and Vinay Prasad, director of the Center for Biologics Evaluation and Research (CBER), highlights that this pathway could accelerate the approval of personalized treatments while bypassing some traditional regulatory requirements.

The initiative was inspired by the case of Baby KJ, a male newborn diagnosed with severe carbamoyl-phosphate synthetase 1 (CPS1) deficiency, a rare genetic disorder that prevents the body from processing protein. Using an expedited single-patient, expanded-access investigational new drug (IND) application processed by the FDA within one week, Baby KJs medical team was able to produce and administer a custom CRISPR gene-editing therapy that corrected the mutation. In May 2025, KJ became the first patient globally to receive a tailored CRISPR-based treatment.

To qualify for this pathway, therapies must target a specific molecular or cellular defect rather than broadly defined diseases. Additionally, the treatment must address the underlying biological cause. While preclinical safety data is still required, this pathway allows therapies to reach patients without prior clinical trials.

Terry Pirovolakis, CEO of Elpida Therapeutics, a company focused on rare diseases, noted that while some elements of the pathway are clear, questions remain about which gene therapies will be eligible. If applied broadly, he suggested it could be transformative for the cell and gene therapy sector.

Interview Highlights

Abigail Beaney (AB): How will this pathway influence gene therapy development?

Terry Pirovolakis (TP): While its not formal guidance, the publication provides a reference point for filing rare disease programs. Ultra-rare diseases affecting just a few thousand patients need dedicated pathways.

AB: Which programs might benefit most?

TP: Programs like Baby KJs, even with only one or a few patients, could gain faster approval. The pathway could also extend to gene replacement therapies, antisense oligonucleotides, and other advanced treatments.

AB: Could this impact commercial decisions for biotech firms?

TP: While it doesnt address commercialization challenges or priority review vouchers, it can help programs reach the clinic faster, potentially paving the way for further regulatory support.

AB: Might companies save on clinical development costs?

TP: Only if their therapies align closely with this pathway. Differences in gene therapy components like promoters or capsids could limit applicability.

AB: Are there still limitations?

TP: Yes. The pathways scope is not fully defined. Critical questions, such as whether it covers different capsids or promoters, remain unanswered.

AB: How does this compare to developments in the UK?

TP: The UKs Medicines and Healthcare products Regulatory Agency (MHRA) has a similar approach, but the coordination between agencies is unclear. Both aim to support rare disease treatments.

AB: Is more support needed for gene therapy programs?

TP: Absolutely. More approved therapies would lower production costs and incentivize additional developments, helping the gene therapy field grow.

This pathway marks an important step in rare disease treatment, though key issues regarding eligibility and commercialization remain unresolved.

Author: Sophia Brooks