FDA official: Agency ironing out the details of plausible mechanism pathway

US Food and Drug Administration (FDA) officials are still “working out the details” of the plausible mechanism pathway being proposed by FDA Commissioner Marty Makary, said Teresa Buracchio, director of the Office of Neuroscience within the Center for Drug Evaluation and Research (CDER), during a Duke Margolis Institute for Health Policy workshop on individualized therapies on Thursday.

The idea for such a pathway was proposed by Makary and Center for Biologics Evaluation and Research (CBER) director Vinay Prasad in a recent article in the New England Journal of Medicine. (RELATED: FDA leaders propose new ‘plausible mechanism’ pathway for bespoke medicines, Regulatory Focus 13 November 2025)

This public workshop examined the science and regulatory environment for these individualized medicine programs, including nonclinical data recommendations, and clinical assessments.

“I think all of us can imagine the day when individualized medicines transform medical care from a general approach to a precision-based approach where treatments are as unique as the individuals they treat. While that day is not here yet, we are getting closer all the time and at lightning speed,” said Amy Comstock Rick, CDER’s Associate Director for Rare Disease Strategy.

Buracchio noted that interest in the field of individualized therapies is growing. In 2018, the agency accepted the first investigational new drug application (IND) for milasen, an individual antisense oligonucleotide (ASO) therapy developed for a young girl named Mila who had a unique genetic mutation causing a form of Batten disease.

Since 2019, the FDA’s Center for Drug Evaluation and Research (CDER) has received over 40 INDs submitted for individualized therapies. Buracchio said that interest in the field further piqued and that “we anticipate rapid growth of the field following baby KJ.”

This recent case study involved a male neonate named Baby KJ, who was born with carbamoyl phosphate synthetase 1 (CPS1) deficiency. This condition prevents the liver from properly processing protein. In this case, the FDA processed an IND within one week, allowing Baby KJ's care team to manufacture and administer three consecutive doses of a lipid nanoparticle treatment. Since receiving the treatment, the patient has been able to process dietary protein and has demonstrated clinical improvement.

Buracchio said that “the experience with baby KJ presents an ideal scenario for the development of an individualized gene-targeted therapy.” In the NEJM paper, Makary and Prasad referred to this case in touting the potential of its plausible mechanism pathway.

Buracchio mentioned that much of the interest in developing these therapies arises from academic centers and non-profit organizations. She also pointed out that there is “clear potential” for the commercial development of these therapies.

Most of the individualized therapy INDs being submitted to FDA involve antisense oligonucleotide (ASO) drug products. While there is potential for other therapies to target these conditions, ASOs and gene therapies offer the “best opportunities for commercialization, even for very small disease populations.”

FDA official: Agency ironing out the details of plausible mechanism pathway

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