August 18, 2020

Overselling stem cells for COVID-19: WSJ article & UMN PR

Overselling stem cells for COVID-19: WSJ article & UMN PR

Many are  jumping on the bandwagon of trying stem cells for COVID-19 or testing other cellular therapies for the novel coronavirus disease, but there have been problems with either the rationales for the trials themselves or more often with how they portrayed. Sometimes there has even been outright hype.

I’ve called this collective trend of promotion of scads of trials of cell therapies for COVID “throwing spaghetti at the wall”. Some may stick, but most probably won’t. If fact, there’s a reasonable possibility that none will stick. That’s just the difficult nature of clinical science even with excellent rationales to start. Yet much of the “cells for COVID” efforts are being at least somewhat oversold. In today’s post I discuss two examples of this problem.

Overselling stem cells for COVID-19: WSJ article & UMN PR
Screenshot of Kimberlin WSJ piece overseeing stem cells for COVID-19.

Hypeful WSJ article on MSCs for COVID

An example of problematic presentation of stem cells for COVID-19 popped up a few days ago in the Wall Street Journal. See screenshot above.

In much of his article The Treatment That Could Crush Covid Osiris co-founder Kevin Kimberlin seems breathless with excitement about the potential of MSCs for COVID. That tone fits with the “crush” in the title. In reality it is not at all a slam dunk that MSCs will even help COVID-19 significantly let alone “crush” it, which implies a cure or game-changing treatment.

The article starts by focusing on anecdotal results on a few patients here and there with no controls.

The second half of the article extols the purported miraculous, almost magical properties of MSCs. Some statements here struck me as hyperbolic and he seems to personify MSCs at times as some kind of superheroes. Here are three examples:

  • “When a MSC detects an infection” Wait, MSCs can detect infections?
  • “MSCs monitor and protect virtually every vessel in our bodies” Do they? I doubt it, but how could you even prove such a claim in humans?
  • MSCs are a “wonder drugstore”. Really? And no risks?

For the average person reading this WSJ article, you’d mistakenly come away thinking that MSCs are the greatest hope for COVID-19. I hope that some specific type of MSCs will be proven to help some patients with COVID-19 beyond the evolving standard of care such as the use of steroids, but again the history of clinical trial research suggests the odds are not particularly high.

Overselling stem cells for COVID-19: WSJ article & UMN PR
Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. The potential of cellular therapies including stem cells for COVID-19 has been oversold in my view.

UMN press release on stem cells for COVID-19 has some issues

A new University of Minnesota (UMN) press release about their trial of mesenchymal stem/stromal cells (MSC) for COVID-19 has some issues that also exemplify the PR challenges more generally in this area.

Don’t get me wrong, I am a fan of the stem cell research at UMN and many of the researchers there, but the PR in this case falls short in some significant ways even if it is nowhere near as problematic as the WSJ piece. Still, the tone suggests a message for readers of the PR that “this is going to work”.

Several other institutions have had similar or more severe issues as well, including the University of Miami, in how they talk about stem cells for COVID-19 trials.

Stem cells for COVID-19 UMN PR: “We’re 1st”

The UMR PR starts (emphasis mine):

“A patient with COVID-19 and lung failure at the University of Minnesota is the first to be treated in the U.S. on a new FDA-approved clinical trial determining the safety and effectiveness of mesenchymal stem cells (MSCs).”

How can you know whether a particular trial is actually the first to have a patient be transplanted with MSCs for COVID-19? You’d have to do a systematic analysis and even then you’d probably have to include a qualifier like “known patient.”

I strongly doubt the statement is accurate in this case. The FDA has cleared many INDs and compassionate use programs for COVID-19 during the pandemic. Most involve MSCs. I also know of quite a few other instances where it seems MSCs were already used in COVID-19 patients, some at universities or biotechs, and sometimes months ago.

Why is it necessary to potentially wrongly claim to be first? Or is the PR claiming the patient was just the first to be treated within their trial? It doesn’t read that way.

The ‘real benefits’?

Another quote in the PR caught my attention:

“In order to determine the real benefit of MSCs in these very ill patients, patients will be randomized to receive three doses of MSC 48 hours apart or a placebo solution.”

It’s great that they are doing a randomized placebo-controlled study, but saying “In order to determine the real benefits” implies, to me at least, that there are definitely going to be benefits and it’s just a question of what type.

A more cautious kind statement would have been something akin to, “In order to test whether there are benefits and what the potential risks might be…” Perhaps they did not mean to imply that there are almost certainly going to be benefits, but I believe the statements should have been more cautionary.

Previous success with MSCs?

The PR then goes on to say that there is a proven benefit of MSCs for other inflammatory diseases:

MSCs have been used successfully in other inflammatory diseases, and single doses of MSCs have been piloted in patients with COVID-19 in other countries, including China and Italy. Prior laboratory research suggests that MSC will blunt the cytokine storm and protect lung tissue from damage from the inflammatory response to the virus.”

As to the highlighted beginning of this quote, which diseases?

Athersys’ MultiStem has proven benefit for some patients with Graft versus Host Disease (GvHD), but MultiStem is not composed of MSCs. It consists of another perhaps somewhat related cell type called MAPCs. Also, while GvHD is in a sense an inflammatory disease, the PR said “diseases” plural. If we assume they are in part referring to GvHD, what are the other inflammatory disease(s) for which MSCs are proven successful?

Also, the word “successful” is a very big claim as it implies proven efficacy and safety.

Take home

It’s very important to be cautious in how one approaches PR and media about a clinical trial, especially during a pandemic. The general area of cellular medicines and stem cells for COVID-19 has had a rough 5 months in my view in terms of failing to be appropriately cautious in how efforts are portrayed. Many people are probably getting the wrong idea about the potential here say compared to treating patients with steroids, which works by a similar mechanism proposed for MSCs but already known to be beneficial for COVID-19.

I’d say if you get regulatory approval to do a trial or start a compassionate use program of some kind of cells for COVID, don’t oversell it upfront. Not only do you risk giving vulnerable people false hope, but you also raise expectations so high that even if you observe some modest, but significant benefit people may be underwhelmed.

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