In my view, it seems likely that the FDA has opened a big can of worms by starting to clear the COVID-19 trials and programs of for-profit stem cell clinics and other related firms.
OK to Stemedica trial
The FDA just approved another such effort, this one by the firm Stemedica. You can read more about previous such COVID-19 cell therapy clearances for the unproven clinic firms Celltex and GioStar here.
The Stemedica trial is similar to some of the other cell therapy efforts for COVID-19 out there in using allogeneic MSCs. The press release says more about the study design:
“The study will enroll up to 40 patients into two cohorts, randomized 1:1 to receive the active study drug plus standard treatment or placebo (lactate ringer solution) plus standard treatment.”
It says that fourteen COVID-19 patients already have received the MSCs via an EUA from the FDA. Stemedica reports they believe there was improvement in this context.
Other, larger biotechs have made similar anecdotal reports, in each case without any controls for comparison.
Why is this a can of worms?
Once the FDA starts giving the green light to unproven clinics for COVID-related offerings, I believe it’s likely that the clinics will use this to leverage their other offerings and perhaps capitalize on the FDA clearance for promotional efforts.
I’ve already seen evidence of this on the web.
Other clinics may submit many more IND applications as well and the FDA may find itself stuck in approving even more because how do they say “no” to a new IND application that is so similar to another one they already approved?
How did the FDA get here?
For Celltex and a non-stem cell clinic biotech firm called Celularity, politics also came into play as their efforts were promoted by Rick Perry and Rudy Giuliani, respectively. That kind of political element is not helpful for the clinical science.
Is part of what’s going on here overall that the FDA has been politically pressured to clear more trials and other authorizations related to COVID-19? A more is better mentality?
Do cell therapies for COVID-19 make sense?
More broadly, while I know some fellow stem cell researchers are on-board with testing stem cells for COVID-19 in many trials, I still wonder about the general rationale of using cells given IV to try to treat COVID-19 via hopefully reducing inflammation.
Relatively cheap, directly-acting steroids have already been shown in many trials to help many patients likely via a similar mechanism.
Sure, infused cells could do more and different things, but we just don’t know if they actually will and cells pose unique potential risks. Then there’s the fact that almost all firms are using allogeneic cells, which in the context of COVID-19 may be more likely to be rejected or cause immune issues. We just don’t know.
The immune modulation sweet spot?
Even if you think the premise of using cells to modulate the immune systems of COVID-19 patients is a good one, how do you hit just the right sweet spot to help the patients? If you overshoot and reduce certain elements of the immune response too much you can harm the patients. Other efforts to increase immunity could make harmful immune responses even worse.
It’s worth pointing out that while Celularity is aiming to boost immunity via NK cell infusions, most of the sponsors using MSCs are trying to go the opposite direction. For example, note this quote from the Stemedica PR (emphasis mine):
“Mesenchymal stem cells that act as a cytokine storm blocker significantly suppress natural killer (NK) cell activation, reducing CXCL1 peptides released by neutrophils resulting in a lesser presence harmful to epithelium and endothelium proteases and oxidants,” said Nikolai Tankovich M.D., Ph.D., Stemedica’s president and chief medical officer. “This results in less damage to the lungs and a better clinical outcome for COVID-19 patients, in particular, for breathing capability.”
So do we want more or less immunity?
Of course, it’s not that simple a question and it likely depends on what stage each COVID-19 patient is in, how severe their disease is, and many other factors. This also highlights the challenges of doing cell therapy trials for COVID patients too where you are likely to have heterogeneous populations of trial participants.