Top FDA official interested in ‘Project Orbis’ for cell and gene therapies

A top official from the US Food and Drug Administration (FDA) said he wants to see something similar to the agency’s Project Orbis program developed for cell and gene therapies, as the involvement of other “high-income countries” could help attract developers, asserted Peter Marks, director of FDA’s Center for Biologics Evaluation and Research (CBER), at the Biopharma Congress on 13 February.
 
At the meeting, FDA officials offered their perspectives on other policy areas, such as the use of accelerated approval for cell and gene therapies and whether the agency is raising its approval standards for new cell and gene therapies.
 
The officials were asked to discuss whether there have been any of lessons learned in developing cell and gene therapy products from the oncology field, and asked to comment on whether cell and gene therapies are now at a similar place where the oncology field was 40 years ago.
 
Marks said that one lessons learned is that to spur the development of cell and gene therapies, it may be best to pool resources and expertise from other regulators in reviewing and approving products, similar to what Project Orbis has done in the oncology space.
 
“A lot of these gene therapies have such small populations that are applicable to the US is if we can expand those markets to other high-income countries, you would attract more developers and cover more diseases,” Marks said.
 
For example, he said a certain rare disease may afflict 20 patients in the US, 40 in the EU and four in Japan. “You would get to this place where commercial viability starts to become real. I think it is important for use to learn what we can,” he said.
 
Project Orbis is an initiative of the FDA Oncology Center of Excellence (OCE) that was launched in 2019 to provide applicants with a framework for concurrent submission and review of oncology products with other regulators.
 
Wilson Bryan, director of FDA’s Office of Tissues and Advanced Therapies (OTAT) commented later in the morning that “there is no question in my mind” that Project Orbis will eventually be expanded to cell and gene therapy products.”
 
Marks added that this could be taken “one step further” and that it could be possible to expand the World Health Organization’s (WHO) prequalification process for new vaccines to new gene and cell therapies. “If it is good enough for us it should be good enough for you.”

In other areas, Marks said that FDA will soon be announcing a new pilot program that would be akin to Project Warp speed for rare diseases, and that a notice about the pilot will soon be published in the Federal Register.  
 
Is CBER tightening approval standards?
 
Marks was asked to comment on whether CBER is tightening its approval standards for cell and gene therapies, as reflected in a growing number of clinical holds for these products.
 
In response, Marks said that some investigational new drug applications (INDs) are “missing major pieces” and that “there are cases where we have bona fide companies coming in” that have problems with their submissions that could be resolved by a simple interactive meeting. Yet he said that CBER does not yet have the “bandwidth” to support all these discussions.
 
Use accelerated approvals for gene therapy with caution
 
In his remarks, Bryan expressed some caution in using the accelerated approval pathway to expedite the development and launch of new cell and gene therapy products.
 
Bryan said supports using the accelerated approval framework for new cell and gene therapies yet pointed out that some these diseases and treatments may not lend itself to this pathway because they are “slowly progressing” diseases. Bryan recently announced he will be retiring from FDA after more than 20 years at the agency.
 
Cell and gene therapies for rare diseases that have a rapid onset may be more amenable to accelerated approval. He added that it can take years to learn whether a new treatment works, and the confirmatory evidence can take five to ten years. He added that “I am worried that we will approve something under accelerated approval that doesn’t work.”
 
He added that he thinks “it will be useful a lot in the future for these very rare diseases.”
 
Biopharma Congress