Marks Outlines CBER 2024 Top Priorities
The top priorities at CBER this year include updating the Center’s tissue guidance to reduce the risk of infectious disease transmission, applying the accelerated approval pathway to rare disease gene therapies, providing general guidance on platform technologies and a guidance on platform technologies specifically for genome editing, according to 0director Peter Marks during a 4/24 Alliance for a Stronger FDA update. He said CBER will also focus on launching a rare disease communication pilot, and advancing its work on a global regulatory collaboration with the European Medicines Agency on doing collaborative reviews to achieve more harmonization on making it simpler for sponsors to submit applications.
Marks’ presentation also touched on a Center-wide initiative to focus on the patient. “I think we want to constantly remind ourselves that we don't come to work each day to push paper and to make the regs look prettier,” he told the Alliance. “But ultimately, it’s to make sure that patients get safe and effective therapies.”
Another area getting attention in Marks’ office is the Center’s upcoming strategic plan for 2026 to 2030. “I think this is going to be a very important strategic plan, not just because of the tremendous development that will occur in the areas that we regulate, but also because I think for some of the management aspects of what we do,” he said. “We will be undergoing a time of tremendous change, not just in how we work in the office or out of the office, but also how we will integrate artificial intelligence into our daily tasks.”
Regarding gene therapies, Marks told the Alliance that while there has been great excitement to see 19 total therapy approvals, there have also been a substantial number of products that have “fallen out of development,” particularly for the smaller of the indications. “I think we really are at a critical juncture due to a combination of factors and a lot of manufacturing challenges with making gene therapies, particularly with adeno-associated viral vectors,” he said.
The clinical development timelines for some of these diseases have been longer than the average venture-funded firm can tolerate, and the different global regulatory requirements have “made it difficult to take a product, which has a marginal return on investment in one country, and essentially bring it to different regulatory environments like the European Union and get approvals there,” Marks continued. The agency is exploring several actions, such as trying to advance manufacturing technologies (platform technologies) and using accelerated approval. “These are small populations where there are no alternatives and I think accelerated approval can be justified easily,” he said.
Regarding accelerated approval, Marks said it’s “ripe for the taking” for small populations in rare diseases where there are great challenges with doing randomized trials, if they can be done at all, and where there is a “biomarker that might be shown very nicely in an animal model to correlate with some clinical outcome.”
Marks said accelerated approval for rare diseases is basically like “taking a calculated risk if we do our risk management correctly… We’re going to make sure they’re high quality and safe. We will make sure they meet an effectiveness standard based on the biomarker or the intermediate endpoint. And then we’ll wait for the confirmatory evidence. I'm not going to lose sleep if it takes two or three years to get the confirmatory evidence because that’s what we're doing by doing this. We're buying the time.”
He said that historically, accelerated approval was the correct decision in about 90% of cases. “And so I think you’ll see us lean into this because if we don’t, I think we’re going to be doing a disservice here.”