The US Food and Drug Administration (FDA) has created a new pathway to bring personalised therapies to market that can bypass certain requirements, using the success of Baby KJ’s treatment as a blueprint.
The new programme, called the “plausible mechanism pathway,” will help the FDA to usher in new and bespoke therapies to market, according to the agency’s commissioner, Martin Makary, and Center for Biologics Evaluation and Research Director (CBER) director, Vinay Prasad, in a New England Journal of Medicine article.
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Baby KJ, a male newborn, was diagnosed with a severe form of carbamoyl-phosphate synthetase 1 (CPS1) deficiency, an inherited rare disorder that causes an inability to process protein during digestion. With a single-patient, expanded-access investigational new drug (IND) application processed in one week by the FDA, Baby KJ’s care team was able to manufacture and infuse a customised CRISPR gene editing therapy that repaired the gene mutation. In May 2025, KJ became the world’s first patient treated with a bespoke CRISPR-based therapy.
Makary and Prasad are keen to use the success of Baby KJ’s case to define the new approval pathway. First, a specific molecular or cellular abnormality needs to be present, as opposed to diseases defined by broad and unclear causes. Next, the therapy in question must target the underlying biological origin and be used for a disease with a well-characterised natural history in the untreated population.
The FDA will also want confirmation that the target was successfully drugged or edited, or both. This can be via animal models or, in some circumstances, non-animal models. Confirmation via biopsy, where clinically appropriate, would also count as supportive evidence for the pathway. Finally, the product will need to lead to improvement in clinical outcomes – the FDA will reduce the threshold for achieving this in diseases with progressive deterioration.
The main feature of the pathway is the lack of requirement for clinical trial data. Expanded access programmes traditionally allow for compassionate use of investigational therapies already under evaluation in clinical trials. The case of Baby KJ highlights the potential to generate critical clinical safety and efficacy data and inform further product development for multiple genetic mutations.
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By GlobalDataThe FDA would move toward a marketing authorisation once the therapy’s manufacturer has demonstrated success across several consecutive patients. Real-world evidence (RWE) will continue to be collected for long-term efficacy and safety confirmations.
William Blair analyst Sami Corwin said the pathway has “broad, positive implications” for cell and gene therapy companies.
“However, based on the language in the pathway’s outline, the application of the pathway, particularly beyond rare and ultra-rare diseases is a bit more unclear,” Corwin added.
While rare diseases will be prioritised on the new scheme, common diseases that have no proven treatments will be considered. For example, Makary and Prasad say a single disease with 150 different genetic mutations would be perfectly suited to the bespoke pathway.
Amid the shift in data towards the post-market setting, Corwin raised concerns as to the level of evidence needed for more common indications.
“It is unclear why the FDA would permit a sponsor to pursue a less rigorous path to market for more common indications in which large, randomised, controlled trials remain feasible and would better quantify benefit,” she said.
In terms of which modalities are included, the FDA officials see no strict criteria.
Makary and Prasad wrote: “Though there is unique enthusiasm about advances in gene and cellular therapies, we see no reason that such principles will not also extend to other drugs over time.
“Nearly 30 years after the sequencing of the human genome, bespoke therapies are close to reality. The FDA will work as a partner and guide in ushering these therapies to market, and our regulatory strategies will evolve to match the pace of scientific advances.”
Advancing personalised therapies has been an aim of the Trump administration as it looks to cut the costs of longer-term treatment. In June 2025, in front of a cell and gene therapy panel, US Health Secretary Robert F Kennedy Jr (RFK Jr) said he was “going to continue to figure out new ways of accelerating approvals for rare disease drugs and treatments”.
A further push in regulatory decisions could come via the appointment of Dr Richard Pazdur as director of Center for Drug Evaluation and Research (CDER). Pazdur is known for implementing several initiatives to expedite drug approvals at the FDA.
In a recent interview with Bloomberg discussing a new framework for personalised gene therapies, Prasad said that “investment into this space will flow”.
However, several pharma companies have already withdrawn from the cell and gene editing space amid poor commercial viability.
Earlier this month, Galapagos wound down its cell and gene therapy division after failing to sell the unit. Japanese pharma Takeda also abandoned its cell therapy research, pivoting instead towards small molecules, biologics and antibody-drug conjugates (ADCs).
Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva.
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