Striking FDA Hahn & Marks JAMA pub on regenerative clinics

It was fascinating to read a new JAMA piece by the FDA on unproven stem cell clinics and other regenerative medicine firms. Many of these guys are profiteering off of buzz about exciting, but mostly unproven technologies. While the JAMA opinion piece reiterates the agency’s commitment to evidence-based regenerative medicine, it also makes some other key points, some of which are newer and worth digging into on a deeper level.

What’s new here from the FDA?

The piece by CBER Director Dr. Peter Marks and FDA Commissioner Dr. Stephen Hahn is entitled, “Identifying the Risks of Unproven Regenerative Medicine Therapies” rightly places the stem cell and regenerative medicine clinic problem in the context of the COVID-19 pandemic. We’ve seen many firms trying to capitalize on the pandemic to make money or generate positive PR. The iffy products promoted for COVID-19 range from exosomes to various kinds of stem cells. Oftentimes there is no particular even common sense link between the product and any logical reason it would help COVID-19.

More broadly, call me skeptical, but so far I just don’t see much reason for excitement about the general idea of stem cells for COVID-19, even that pursued by legit biotechs.

So what are the key points of Marks & Hahn here? What does the article mean in the real world?

I’m going to highlight a few passages that struck me as particularly meaningful.

The authors also include a Box of key bullet points, which you can see in a screenshot below.

Point 1. Adverse events drive FDA action.

From the article:

“The increasing number of adverse events being reported following the widespread use of unapproved regenerative medicine therapies at hundreds of clinics across the country make it necessary for the FDA to act to prevent harm to individuals receiving them.”

My interpretation of this is as follows. When it comes to the regenerative medicine space, the FDA is guided by patient safety issues and can be driven to action by concrete evidence of patient harms. The “make it necessary to act” part here is very strong and the “to prevent” part should be a clear signal to many clinics, even those not linked to concrete harms yet. I always keep hoping for more proactive rather than reactive steps by the agency.

Point 2. Many clinics sell unapproved cellular drugs, which is illegal.

From the article:

“Unapproved regenerative medicine therapies are concerning precisely because they have not been treated as what they are: investigational therapeutics for which evidence for safety and efficacy is not available.”

While they don’t say as much, my reading of this is that many offerings are unapproved drugs according to the FDA. The agency really cannot tolerate widespread use of risky, unapproved drugs of any kind or such tolerance risks undermining their overall mission and authority. Further, the offerings are often not backed up by good data.

Point 3. FDA suggests there’s more harm than we know so far.

From the article:

“Because these unproven regenerative medicine therapies are being administered without regard to the FDA’s regulatory oversight, it is impossible to know with certainty the number of individuals who have experienced serious adverse events following their administration.”

Often clinics or their advocates have challenged me, “where’s the harm?” While we know more than we used to about bad outcomes, it’s great to see the FDA acknowledging that the scope of harm isn’t clear and by extension is likely much wider than we know.

Point 4. The FDA says it needs help, wants engagement

From the article:

“However, the agency needs the engagement of both clinicians and patients to help to ensure that instead of remaining unintentionally or intentionally hidden, potentially harmful unapproved regenerative medicine therapies are identified and removed from the market.”

This passage seems particularly striking to me in a few ways.

First, while I agree that some clinic firms actively try to avoid being on the FDA’s radar screen and so may be “hidden”, there are on the other hand ample data, some of it from me and Leigh Turner as well as others, that should help inform the FDA about the specifics of hundreds of clinics.

Furthermore, while we do not know how many untitled letters the agency has sent to clinics, I doubt it is above 100, and by comparison there are likely 1,000 clinic firms out there. Okay, so not all these clinics are non-compliant even if they sell scientifically unproven offerings, but even if you say 700 are probably noncompliant, then the FDA already has ample info on these and should send more letters without any help.

Speaking of help, the second thing about this quote that struck me is that the agency is asking for the community engage with it. Although the FDA in the last 3 year has been far more interactive, in its longer history it has been much more difficult to connect with and get meaningful dialogue going. Given this larger historical context, it’s wonderful to see the agency actively saying, “we need info from you!” to the community.

Finally, it’s quite possible that the FDA is aware on a general level that there are many more, perhaps hundreds more, firms out there in this space that have not yet been documented by researchers.

Looking ahead: part of the core mission

Practically speaking I don’t know how much an article like this changes things, but I see it as a positive overall and likely to spark some helpful shifts out there. Their article ends strongly circling back to the core FDA mission and indicating the clinic industry poses a risk to that.

To me this means the agency is taking this very seriously. This is further underscored by the agency leadership taking the time during the COVID-19 pandemic to write this when they are beyond busy with other issues.

So much has changed from even just 4 years ago when the FDA didn’t seem engaged at major level with this problem. Whether you agree or disagree with the FDA on regenerative products, it’d be wise to pay attention to what they are saying and doing, especially if you are producing and/or selling a product of this kind.