FDA Issues Guidance on Individualized Medicines

When the New England Journal of Medicine in October 2019 published a study on an effort to develop an individualized therapy for a child with an ultra-rare neurodegenerative disease, U.S. Food and Drug Administration officials wrote an accompanying editorial that explored the implications of the work.

The editorial recognized that academic clinician–investigators were capable of quickly identifying a genetic mutation behind an ultra-rare disorder and producing an antisense oligonucleotide to address it. They recognized others were following suit and that the potential was there to do the same with gene and cell therapies.

The editorial, though, focused on questions that the development of these individualized therapies raised rather than any particular action that the agency would need to take in response to their emergence. They included questions of what type of evidence will be needed before dosing a human with an experimental therapy, what assurances of safety will be necessary, how compelling mechanistic data must be, how doses should be determined, how well characterized a product will need to be, how efficacy should be evaluated, and what role the urgency of a patient’s situation should play in the regulatory decision-making process.

Now the FDA is weighing in with its first guidance addressing the question of individualized therapies. The draft guidance is focused on investigational new drug submissions for individualized antisense oligonucleotide products.  

“Developing these products – also referred to as ‘n of 1’ therapies by some because they are designed for a patient population of one person – brings a set of challenges and considerations not seen with the typical drug development process,” said Patrizia Cavazzoni, acting director of the FDA’s Center for Drug Evaluation and Research.

Cavazzoni noted these therapies are often designed to treat a patient with a rapidly progressing condition in need of prompt intervention. They also may be developed by academic investigators, rather than by biopharmaceutical companies. As such, the investigators may not be familiar with the FDA’s policies and may have no experience interacting with the agency.

The guidance addresses how to obtain feedback from the FDA, the process for making a regulatory submission, requirements for Institutional Review Board review, and how to obtain informed consent. The agency is currently seeking comments on the draft guidance.

“The FDA understands that we’ll need to work together with the developers of these drug products to bring them safely to patients, and we are willing to engage as needed to address the challenges,” said Cavazzoni.
For patients with ultra-rare conditions, individualized therapies may be their best chance of getting a viable treatment to halt or reverse their disease. Several efforts are underway to make this economically viable and possible in a rapid timeframe.

Though the agency will have much ahead of it as it addresses questions of how to best address regulatory questions around individualized therapies, it has been quick to recognize the speed with which the area is developing. This is a positive development that will further progress this area.