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Overview of FDA meeting on embryonic stem cells: cautious movement toward the clinic
On Thursday, an FDA advisory committee meeting met to figure out how to decide whether products derived from embryonic stem cells were ready to be tested in human participants. There was much talk, even more questions, and no firm decisions.
Even so, the attendees I spoke with told me they felt certain that the FDA was serious about moving stem cells to the clinic. One consultant said that previous to today’s meeting, investors had expressed worries that today’s meeting would serve to kill the field. Several years ago, patient deaths in gene therapy trials caused the FDA to halt all such trials under its jurisdiction, another consultant told me, and that field has never recovered.
Now, the consensus was, the agency seems cautious about moving forward, but not spooked. Three companies, Geron, Advanced Cell Technology, and Novocell described their work bringing embryonic-derived cells in (respectively) acute spinal cord injury, visual impairment, and diabetes. One expert who wasn’t on the committee said that the discussions had been impressively grounded in science, even getting into specifics about what assays might be considered. Attendees were surprised that no opponents of embryonic stem cell research showed up, but the FDA's announcement said explicitly that it was only the cells' safety that was under consideration.
The director of the FDA’s Office of Cellular, Tissue, and Gene Therapies Celia Witten called the meeting useful. “We got enormous information in three areas: preclinical, product characterization, patient monitoring.” She added that within each area there were lots of recommendations. She declined to speculate on when or if a guidance document would come out, but it didn't seem soon.
But the recommendations were really approaches to answering lots and lots of questions. How do we know what cells we have? How do we know what the cells will do in the body? Where do you put cells? Where do they go? What do they do? How many cells might be dangerous? How many can be useful? What can animals tell us? If the cells “go rogue” in a human participant, will we be able to stop them or even to track them? What’s the best way to balance risk and benefit?
“I don’t know that there’s a one-size fits all answer,” said committee member Steven Goldman, a professor of neurology at University of Rochester Medical Center. At the time, he was making the point that different stages of differentiation will be appropriate for different diseases. (Neurodegenerative diseases may need progenitor cells that proliferate and integrate; diabetes seems best off with fully differentiated islet cells.” Still, the notion “it depends” applies to disease, cell type, patient characteristics, delivery route, etc. etc. ( See our interview with Marie Csete, head of the California Institute of Regenerative Medicine, which is also wrestling with these issues.)
I thought attendees would be disappointed in this attitude. After all, aren’t researchers reaching for the clinic looking for the list of assays they need to do to put cells into human subjects? But I spoke with four people, including Witten, and everyone seemed quite satisfied; that every product was already assessed individually no matter what it was and that potential risks always had to be titrated to potential benefits.
In the open public session, Amy Rick head of the Coalition for the Advancement of Medical Research asked the committee to consider the risk of living with and dying from a horrible disease when assessing risks to clinical trial participants; that’s a tough request, since the earliest trials set out to show safety rather than efficacy.
Other issues will need to be wrestled with if ES-cell therapies move from potential experimental procedure in human participants to potential therapies: providing access to care and applying treatments to a heterogeneous population. Its roots can be seen in the attendees, mostly white, with a smattering of Asian. The mixture of men and women attending was slightly tilted to men, more so on the advisory panel. Most people seemed closer to 60 than to 30.