Expanded Markets, Accelerated Approvals to Bring Gene Therapy into the Mainstream

Peter Marks, MD, PhD

Peter Marks, MD, PhD, director, Center for Biologics Evaluation and Research, FDA, was the keynote speaker at the 2023 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, March 19-22, in Dallas, Texas. His address focused on steps that have to be taken to support gene therapy’s emergence into the market, including improving roadblocks with manufacturing, clinical trial, commercial viability, and regulatory processes.

CGTLive spoke with Marks to learn more about these issues and potential strategies to address them, including the accelerated approval pathway and the use of surrogate endpoints. He also touched on gene therapy’s progress in the last decade up to data presented at the MDA conference and other challenges.

CGTLive: How can we make gene therapy a reality?

Peter Marks, MD, PhD: We need to address some key things that get in the way of getting gene therapies to patients, 1 of them is that manufacturing is still quite expensive and complicated for these products. We need to try to address that. Another is how to move these therapies through clinical trials in a relatively facile manner, making use of what we have at our disposal in at the agency, like accelerated approval using surrogate endpoints, such as biomarkers or intermediate endpoints, in order to get an initial approval, which we then confirm with a clinical endpoint, such as function or survival, ultimately showing that there's real clinical benefit. Finally, there's the issue of how we make sure that there's commercial viability for these products. And that has to do not only with reducing the cost of manufacturing, but also potentially helping to expand the market from just a US market to a global market. If we can help get some regulatory convergence, so it's easier for the development of rare disease therapies to not just be approved in the US initially, but to be approved in several different countries simultaneously, that may bring the market size up to more commercial viability. Not just one country will benefit; everyone benefits.

Is there any research being presented at MDA that is particularly exciting to you?

In general, I think that it's just a very exciting time for gene therapy, especially since gene therapy for neuromuscular diseases has the chance to be transformative. We've seen, for instance, with spinal muscular atrophy type 1, how gene therapy transformed a uniformly fatal disease into a disease now, where if children are treated early enough, they can develop normally. I can't tell you what it's going to look like 20 years from now, but if you're a parent of a child, who's 4 or 5 years old, who otherwise would not have been here with us, and nowthey're a healthy 4- to 5-year-old. That's almost like a miracle. So, I think it's a truly exciting time in this field.

There are medicines that have been used, for instance, in Duchenne muscular dystrophy, like prednisone, which doesn't really get at the underlying disease, whereas a genetic therapy potentially corrects that underlying problem or partially corrects the problem. And that can make all the difference in the world, hopefully, over a longer period of time with fewer side effects.

What are some of the challenges or needs in this space that you've seen highlighted at this meeting?

I think, obviously, resources are always an issue. I think people are trying to address the challenges here. Some of the challenges are having enough sites that will be ready to give gene therapy when it's ready to be given. And I think the MDA is trying to address that with specialized care centers. We also need to continue to educate people about this because education is not something to be underestimated. From other experiences I've had at the FDA, I know that if we don't educate the community about the potential value of gene therapy, aside from the kind of leading edge people who are excited about new things, other people may not come along or it may take them much longer than it would otherwise to come get therapies that could potentially really bring them benefits. So, I think the kind of education that the MDAis able to do is really important.

Transcript edited for clarity.

REFERENCE

Marks P. Keynote address. Presented at: 2023 MDA Conference, March 19-22; Dallas, Texas.