‘We’re open for business’: FDA’s Peter Marks says agency ready to review novel cancer vaccines despite unknowns
As new cancer vaccines—led by Moderna and Merck’s mRNA-4157—near pivotal trial readouts, the FDA’s vaccines czar Peter Marks, M.D., Ph.D., said the agency is ready to review the shots despite AI-related unknowns.
“We are ready to review—we’re open for business,” Marks, director of the FDA’s Center for Biologics Evaluation and Research, said of cancer vaccines at the 2024 World Vaccine Congress (WVC).
“We have therapeutic cancer vaccines coming in; I think we would review them very much like we could review potentially a CAR-T cell or other therapeutic products,” Marks said.
The FDA has approved a cancer vaccine before, namely Dendreon’s prostate cancer shot Provenge. Although the next wave of therapeutic cancer vaccines aim to prove efficacy through familiar clinical endpoints—such as tumor progression and overall survival—the novelty of their tech raises new regulatory questions. And neither the FDA nor the biopharma industry seem to have the full set of answers right now.
For the production of CAR-T therapies and Provenge, a patient’s own immune cells are collected and then manipulated to recognize cancer cells. In both cases, although the final products differ based on the patient’s cells, the starting components and the processing steps are the same in nature.
For Moderna and Merck’s mRNA candidate mRNA-4157, though, AI dictates how the individualized vaccine should be formulated to attack cancer.
The platform sequences a patient’s tumor and healthy tissue and then uses AI to capture the most relevant tumor-specific mutational signatures. Neoantigens identified this way form the basis of the vaccine construct, and the resulting proteins can be very different between individuals. The goal is to induce an immune response against tumors bearing those biomarkers.
As AI is a core component of the program, Moderna expects the FDA will need to inspect its algorithm as part of the review of vaccines like mRNA-4157, also known as V940, Kyle Holen, Moderna’s head of development of therapeutics and oncology, told Fierce Biotech on the sidelines of WVC.
“We have to put our algorithm on a hard drive, put it in armored truck and have it shipped to the FDA,” Holen said.
AI algorithms are known to evolve as they absorb new information. But to protect the integrity of a clinical trial for an AI-based vaccine, Moderna had to “lock down” the algorithm before the study to avoid any changes that may have confounded the results, Holen added.
All of this raises a new regulatory question: How much change to the AI algorithm is allowed before the vaccine should be considered a completely new product?
“We don’t know,” Holen said. “Nobody knows. We’re in, like, no-man’s land here, because no one’s ever done this.”