The FDA has approved 12 gene therapies so far, and the agency's top drug regulator wants to see the road ahead illuminated with green lights.
If the FDA only approves two or three per year over the next few years, Peter Marks, M.D., head of the FDA’s Center for Biologics Evaluations and Research (CBER), says "that’s a failure.” His comments came at a webinar Tuesday hosted by the Alliance for a Stronger FDA, a lobbying group for the agency.
“Success would be … if not exponential, at least some logarithmic progression towards more and more gene therapies being approved,” he said. The agency has approved 12 gene therapies to date, according to Marks, five of which came in 2022.
To get there, Marks and CBER have a four-poin plant: improve manufacturing through new research, clarify the use of the accelerated approval pathway for gene therapies, coordinate regulatory decisions with other regulators and launch an Operation Warp Speed for rare diseases. Easy, right?
Here’s the hitch: Executing these goals requires adequate staffing, a perennial issue for the agency that’s long struggled with one of the widest revolving doors in government. Marks said that while the latest user fees reauthorization expanded head count, talent is constantly being poached.
“[W]e still also have to deal with the challenges of a staff that is in high demand in private industry, particularly in the areas that we most want to retain,” he said, highlighting gene therapy and chemistry, manufacturing and controls as areas of focus.
But fending off enticing job offers is a given. Allowing innovation in the drug industry to lap regulators’ efforts is not. Marks underscored that making the manufacturing process for gene therapies more efficient is a critical next step, saying that the agency is working on funding grants that could go toward automating the process. One proposal by Marks is to streamline the regulatory review of the viral vectors used to deliver gene therapies, including toxicology and manufacturing information.
His words and proposals come as exorbitant development costs and small commercial markets have thwarted past efforts by companies and foundations to make lifesaving treatments available even when the science is compelling. Marks commended these efforts and says the agency must support them.
"I am incredibly grateful for the foundations that are trying to work on gene therapy now, but they're struggling like salmon swimming upstream,” he said.
The reality, however, is that Marks’ gene therapy reforms are but one ball among many that the center is juggling. Namely, CBER continues to manage an onslaught of COVID-related work. Marks said the U.S. will be “laughingstocks” if it does not build and maintain a national surveillance system for infectious diseases and that there are currently significant data gaps as a result of heavy reliance on state-by-state reporting.
“I'm sorry, but the nightmare is not over,” he said. “Just because you had a nightmare last night doesn't mean that you can't have one tomorrow night.”
He said the amount of work left to the agency remains significant, as emergency use authorization applications morph into full approval applications, requiring more detailed regulatory analysis. The agency also has to stay on top of the latest circulating virus variants—a nod to Marks' surveillance qualms—so that manufacturers can update vaccine formulas to the most prevalent strains. Marks says on top of all of this, CBER and the FDA need to keep their eyes on other viruses of concern to prevent being caught flatfooted in the event that a new disease spreads quickly.
“The way we were able to actuate Operation Warp Speed was by, essentially, pulling people from other projects, and we’ll need in the future to think about ways to avoid having to do that,” he said.