FDA OK’s more COVID-19 efforts of unproven stem cell clinics

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

FDA, can of worms, COVID-19
Is the FDA opening a big stem cell clinic can of worms related to COVID-19 clearances?

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.

Note that I’ve covered Stemedica in the past and had some ongoing concerns. A KPBS investigation raised some other troubling issues too four years ago.

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?

COVID-19 Politics

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.

11 thoughts on “FDA OK’s more COVID-19 efforts of unproven stem cell clinics”

  1. It is unfortunate that you took up on yourself a responsibility to judge about how the FDA is giving permission for clinical trials with investigational products. I am not sure if you are familiar with an IND submission and if you ever got one. It is not the first time you were mudding Stemedica by getting information as in the past through a “grape vine” channel. Stemedica provided cells for free for 14 patients on the requests of physicians applying for Emergency INDs for patients in life-threatening cases when other options did not work. Our initial observations were important to ask for permission to run a clinical trial to confirm our findings. The Stemedica trial design is similar to some of the other cell therapy efforts for COVID-19 out there in using allogeneic MSCs, but not all MSCs are the same – you should learn that! You are asking “Do cell therapies for COVID-19 make sense? It is a great effort to running clinical trials and by doing just that we will give you the answer to your question. Finally, what did you do to help COVD-19 patients?

  2. Gerard A Malanga

    You are STILL to biased against these treatments when you blog. Try to offer a more balanced opinion before you make your statements. Also be aware of the same issues with current treatments offered by Pharma . Still much to be “proven”. If these companies are going to the FDA for an approved FDA trial, what is your issue with that ?

    1. It’s relevant when firms have a complicated history to consider that as context for what’s going on now. I don’t hold it against them for getting FDA clearance at all, but I also wonder and question some of what is going on at the FDA now when it comes to COVID-related decisions.

  3. Dear Paul, thanks so much for highlighting these important issues. Indeed, not just potential adverse effects on cellular immunity should be kept in mind, but also undesireable triggering of the innate immune cascade systems in the blood (eg coagulation/clotting and thrombosis) are to be considered in particular when INFUSING cellular therapies (eg MSC products) with highly variable prothrombotic Tissue Factor (TF/CD142) expression into hypercoaguable COVID19 patients who frequently display micro and macro thrombosis at autopsy; Adequate counter measures such as appropriate thromboprophylaxis should be taken: https://www.frontiersin.org/articles/10.3389/fimmu.2020.01091/full “MSC Therapies for COVID-19: Importance of Patient Coagulopathy, Thromboprophylaxis, Cell Product Quality and Mode of Delivery for Treatment Safety and Efficacy”.

  4. Bravo to the FDA. Thankfully, it has come to understand that during exigent circumstances bold action is required. I can’t wait for the first SCT product to be approved for COVID. It will be a truly monumental day for all Americans.

    1. @Rahman,
      A pandemic does call for bold action at times, but does it make sense to have dozens of trials (and compassionate use programs) of MSCs and other cells, sometimes without the sponsors have their own rigorous data? What if the vast majority are proposed to work the same way as steroids? What if some of the sponsors’ past behaviors were arguably problematic in some serious ways?

      1. I understand your concern but we have to understand that things change. Paradigms change. Models change. When faced with such a transformative medical episode, certain standards of yesterday necessarily become the anachronisms of today. Progress – scientific or otherwise – is rarely perfect, but to ignore the medical imperatives of our current moment by clinging to business-as-usual would itself be reckless. Purposeful, thoughtful regulatory and clinical trial reform for SCT products is the way forward.

  5. @Paul, can you point to a placebo controlled clinical trial or an FDA approval (not just an Emergency Use Approval) that proves your statement?…

    “relatively cheap, directly-acting steroids have already been proven to help such patients likely via a similar mechanism.”

    Thank you.


    1. @WST, Just one example of supportive literature on trials:
      “Use of inexpensive, readily available steroid drugs to treat people hospitalized with Covid-19 reduced the risk of death by one-third, according to an analysis encompassing seven different clinical trials conducted by the World Health Organization and published Wednesday in the Journal of the American Medical Association.”
      But it’s possible you’re still right that “proven” was a little too strong a word so I revised it a bit.

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