FDA plans to launch communications pilot for promising rare disease gene therapies

The head of the US Food and Drug Administration’s (FDA) biologics center said the agency will soon launch a pilot to apply the lessons it learned from the COVID-19 pandemic to accelerate development of certain gene therapies for rare diseases.
 
Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), said his office is trying to find ways to accommodate companies who are developing treatments for rare diseases. One of the ways they are trying to help companies is by giving promising rare disease gene therapy developers a chance to increase interactions with the FDA during the development phase.
 
Speaking virtually during the FDA Rare Disease Day 2023 on 27 February, Marks noted that “some good” has come out of the pandemic because the agency was able to learn how to improve communications with drug and vaccine companies developing critical COVID-19-related products.
 
"There were things that we learned from working with industry while we were making medical countermeasures that actually do potentially apply to rare diseases,” said Marks. “During the pandemic we had very constant contact with many of the manufacturers where we essentially threw out the way we normally do meetings and had a constant back-and-forth almost on a day-to-day basis when issues arose. We want to see about doing a similar thing with rare diseases.”
 
While he wasn’t more specific, Marks said that FDA is preparing a “Communications Pilot” that promising rare disease manufacturers can participate in. It would give them the opportunity to have increased discussions with the agency about their product and hopefully help get their product through the development, review, and marketing process faster.
 
The purpose of the pilot would be to speed the pace of therapeutic development for small populations with high medical needs. Products that would be eligible for the pilot would be those that recently received regenerative medicine or breakthrough therapy designation and are preparing to enter pivotal clinical trials.
 
Marks highlighted the number of challenges that rare disease gene therapy developers face. When it comes to non-clinical development of treatments, he noted that many rare diseases don’t have animal models to use and even if such models exist, there is a need for human cell lines or human organoid models that are hard to come by. He was optimistic that there are more organoid models now that are helping researchers develop new gene therapies for rare diseases.
 
Marks also noted that FDA is looking into certain tools such as Bayesian statistics to design clinical trials so developers can make use of every patient enrolled in their trials.
 
One of the biggest challenges, according to Marks, is that even if there is a potential treatment, it’s often not feasible for manufacturers to produce them for a very small population. He said that manufacturing has “turned into a real bottleneck.”
 
"One of the issues here is that manufacturing of gene therapies has really been something that's been quite costly, it's not standardized, and it has led to a slowdown from being able to move from a gene therapy concept to treating patients," said Marks.
 
 
Because of that issue, Marks said the FDA is working with the National Institutes of Health (NIH) to establish the Bespoke Gene Therapy Consortium, a public-private partnership involving multiple companies, non-governmental organizations and government agencies, which is looking at ways to standardize and enhance production of gene therapies.
 
According to Marks, the first focus of the consortium is to look at adeno-associated virus gene therapies because they’re the most common vectors being used for directly administered gene therapies, but the hope is that kind of research will branch out in the future. Ultimately, he said the idea is to create a playbook on getting treatments from concept to manufacturing.
 
“Due to cost of capital investments and protecting intellectual property, most gene therapies require treating at least 100 patients a year in order to break even,” said Marks. “Any less than that and the treatments fall off the market he added which has happened in Europe a number of times.”
 
Marks noted that any one country may not have enough rare disease patients to make it viable to research a treatment but that aggregating patients from different countries may improve the odds.
 
CBER is hoping that by bringing regulators across the globe to harmonize their work, they will improve the viability of gene therapies. The center thinks that automation in manufacturing can also help bring down costs and is giving grants to various academic institutions to explore that idea.
 
“We also want to try to help move forward use of accelerated approval in this area,” said Marks. “There have been some controversy in this area about accelerated approval but I think it’s pretty clear for rare diseases, particularly in the enzyme replacement area and neurodegenerative diseases, the only way we’ll get there for small populations if we consider the well-thought use of accelerated approval or we look at a biomarker, for example enzyme levels, for an enzyme replacement.”
 
Marks also pointed to the FDA Oncology Center of Excellence’s (OCE) Project Orbis, which was launched in 2019 to help development of cancer treatments as a model to emulate for rare diseases. (RELATED: Top FDA official interested in ‘Project Orbis’ for cell and gene therapies, Regulatory Focus 13 February 2023)