Individualized Therapies: CBER Director Discusses Challenges, Regulatory Approach

Regulatory NewsRegulatory News
| 03 March 2020 | By Michael Mezher 

The US Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER) is looking for ways to facilitate the development of more products intended to treat individual or small groups of patients, including cell and gene therapies, antisense oligonucleotides and phage therapies.
At a workshop at FDA’s headquarters in Silver Spring, MD on Tuesday, CBER Director Peter Marks addressed some of the barriers to developing individualized therapies such as “customized products” with a single indication and a mode of action that are tailored to individual patients, or “created products” that could target different indications via different modes of action.
Marks noted that there are “probably some regulatory distinctions between these two classes.”
The workshop comes after the landmark use of an individualized antisense oligonucleotide therapy was documented in the New England Journal of Medicine last year. In an accompanying editorial, Marks and Center for Drug Evaluation and Research Director Janet Woodcock raised questions about how these so-called “n-of-1” therapies would be regulated.
According to Marks, one of the biggest challenges to developing gene therapies for small populations is in manufacturing. Marks noted that while second and third generation genome editing tools have been developed, vectors are being produced “much the same way that we made them at the turn of the millennium.”
“The setup costs, currently, to make a gene therapy for 20 people are very similar to the setup costs to make a gene therapy for 200 people, in terms of commercial process,” he said.
Marks also cited challenges in nonclinical and clinical development when considering products developed to treat a single patient or very few patients.
“No one is suggesting that for these products we’re going to have traditional Phase 1, 2, 3 development. The question is where we can go with these to end up with products that are safe and effective,” Marks said.
For nonclinical development, Marks said researchers should look to alternative models, such as human organoid systems and humanized mice, because traditional animal models may not be appropriate for treatments involving genome editing.
Marks joked that while some people might think he looks like a mouse, his genome “does not look exactly like a mouse and it’s a real problem.”
On the clinical side, Marks said we need “novel ways of thinking for small populations,” including new approaches to documenting diseases and natural history so that investigators can tell when there is a change from baseline.
Marks also suggested that a new approval model could be used for individualized therapies, such as a “continuous reassessment model or some other statistical method—a Bayesian or other design—to see if there’s some point … where one declares victory that you actually have an effective product.”


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you

No taxonomy