In February, the news broke that the Food and Drug Administration (FDA) had approved a “first of its kind” new cancer therapy. Iovance’s AMTAGVITM, the subject of the approval, is a personalized immunotherapy for advanced melanoma. To be treated, adult patients who are ineligible for surgery or have metastatic disease provide their tumor cells to their medical team. Tumor-attacking T-cells are isolated from the sample, grown and multiplied in-lab, and re-infused into the patients for a turbo-charged immune response that, according to clinical trial data, have shown promise in shrinking patients’ tumors. This drug joins a list of others that work something like this: Patients provide cell samples, which are then isolated and modified or expanded in-lab, and then eventually infused back into their bodies. This general patient experience, though, indicates a different model from what we have seen before. These “living drugs” use your own cells, but better, to fight these daunting battles.

These treatments paint a different picture from the more traditional “pill” or one-time injection experience, especially because of the personalized nature of the final infusion—an engineered or expanded version of your tissue. Add stem cells to this equation, and we’re looking at adaptable regenerative tissue therapies. Personalized medicine and ‘living drugs’ like these define the space that emerging technologies in regenerative medicine hope to occupy as they move from bench to bedside.

Exciting as this is, cell therapies face complex regulatory schemes and various levers to the process of FDA approval. In the approval process, we deal with two main levers: product classification and approval timeline. Amtagvi was approved as a drug, and with pace using the Accelerated Approval pathway before the completion of Phase III clinical trials. Because it was one of the first approvals of its kind, it also qualified for an combination of speed-generating FDA levers: the Regenerative Medicine Advanced Therapy (RMAT) designation, fast track and priority review, and orphan drug designations. These fast-tracks often relate to the therapy’s effects on potential patients: for example, are the intended patients part of a rare disease population? Are they classifiable as regenerative therapies for life-threatening conditions?

A preliminary question before the FDA approval odyssey is what type of products these therapies are. The FDA regulates food additives and “drugs and devices” but this latter designation is functionally split out into drugs, medical devices, and biologics (products derived from living sources). When the characterization is fuzzy, combination products can include approval/documentation elements from more than one category. Cell therapies, and other regenerative medicine therapies, might find themselves squarely in the RMAT umbrella, but their creators still need to figure out what kind of product they are and how to seek approval accordingly.

This confusion over product classification and pathway selection is not just confusing within the FDA, it’s becoming a problem vis-à-vis FDA jurisdiction and regulatory latitude. The Ninth Circuit, just last month, heard oral arguments in a case on appeal between the U.S. government and a private stem cell clinic in California. The government argues that the clinic’s services—therapies and products derived from stem cells that purport to treat a variety of diseases— are subject to FDA regulation by constituting “drugs.” However, the clinic raises a “surgical procedure exception” to claim it falls outside FDA purview as a surgery, not a drug. The procedures in question? Removing stem cells from patients, isolating and processing them in lab cultures, and re-introducing them back into patients. The lower court in this case found that the determination of whether a therapy counted under the surgical exception was a question of fact. This opens the doors to litigation and dispute between, especially, private entities and the FDA, over what would count as regulated therapies or non-regulated surgical procedures. This puts the technical surgical/drug distinction task in the hands, ultimately, of non-expert judges. If the Ninth Circuit upholds that ruling, there may be a circuit split because the 11th Circuit previously ruled on very similar facts that these therapies were drugs.  This uncertainty calls into question the FDA’s regulatory latitude over therapies relatively similar, if not incredibly similar, to the Amtagvi and Casgevy “experiences.”

Possibly opening the door further to courts weighing in on the matter is the FDA’s relatively weak regulatory structure when it comes to cell therapies and regenerative medicine products. A Technology Assessment from the Government Accountability Office identified several areas for policy development with therapies like Amtagvi and even cell-based tools like organoids. These included standards development, FDA-industry transparency for increased access of regulatory expertise, and reconsiderations of the existing combination product/medical device pathway designations to accommodate, or create a new category for, these therapies. Notably, the GAO report was targeted at congressional committees to spur continued legislation and regulation in this space. This follows legislation like the 2016 21stCentury Cures Act, which saw pointed criticism over what some described as lax regulations and standards for regenerative therapies. Ultimately, the existing structure attempts to fit a square peg in a round hole; cell therapies, let alone stem-cell-mediated therapies, are distinct enough from manufactured drugs, biologics, and devices to constitute their own designation. The FDA ought to consider exercising its authority to establish a separate category for cell therapies, allowing add-on pathways like the RMAT designation to fast-track such therapies, not define the therapies themselves.

Even if FDA regulatory action is the best next step forward, the story may be a bit more complicated in practice. Today’s climate seems to include more skepticism and more limited regulatory latitude. And yes, this includes the FDA. The 2024 Supreme Court docket offers several high-profile, high-stakes cases challenging Chevron deference and agency decision-making, and a direct challenge to FDA approvals when squared with state abortion laws over the drug mifepristone. How these cases shake out will likely have a major impact on the role of FDA decision-making when squared against questions of science, biological ethics, and politics in a burgeoning new area of medicine powered by stem cell research.

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