How Scott Gottlieb may transform the FDA’s approach to stem cells

The Trump FDA commissioner nominee Dr. Scott Gottlieb Dr. Scott Gottliebcould dramatically alter how the agency regulates investigational stem cell therapies. How might such changes unfold? There are potential upsides and downsides to  the seismic shift that could be in the offing.

Gottlieb has written in the past about his perception of FDA over-regulation of stem cells such as in this piece in the WSJ. There he made a number of assertions that signal his view at least back then that when it comes to regulation of stem cells by the FDA, less is more.

More recently, a speech he gave at an ISSCR meeting in Berkeley last year is much more balanced in tone than the 2012 WSJ piece. This quote from the Berkeley talk, for example, is balanced and emphasizes standards:

“Expediting the development of these novel and transformative technologies like gene- and cell-based therapies doesn’t necessarily mean lowering the standard for approval, as I believe other countries have done. But it does mean having a framework that’s crafted to deal with the unique hypothetical risks that these products pose.”

Still that WSJ article is concerning.

For instance, he and his co-author Coleen Klasmeier, both former employees of the FDA, strongly criticized a federal court ruling in 2012 that the FDA could regulate laboratory-proliferated stem cells as a biological drug. Oddly, much of the basis for their criticism was far broader than the reality of the court ruling. They suggested, for instance, that the ruling opened a veritable Pandora’s box of FDA over-reach potential that extended to all autologous uses of stem cells (lab-grown or not) and beyond, but that was not the case as the ruling was focused on lab-grown stem cells. Even so they made largely unsupported generalizations such as the following:

“If the FDA’s victory is upheld on appeal, then conceivably nothing done as part of clinical practice is beyond the agency’s reach.”

In the intervening years since the 2012 court ruling and the WSJ article, we have seen that the sky hasn’t fallen from the FDA having obtained the defined authority to regulate lab-expanded stem cells as drugs. In fact, oddly enough if anything the more time that has passed, the less inclined FDA’s CBER biologics branch that oversees stem cells has been to take action on stem cell biologics. It’s hard to view the FDA issuing less than one warning letter per year to stem cell clinics even as there are upwards of 600 of these clinics as a form of overreach.

From a scientific and medical perspective, there are good reasons to regulate lab-grown stem cells as drugs. The cells are known to change their differentiation properties, accumulate mutations and epigenetic changes, and undergo other significant alterations in the dish in the lab. There is also, perhaps more directly related to the FDA’s mandate on biologics, substantial potential for contamination of cells in a lab during proliferation.

Since 2012, another big change has been the explosion of adipose stem cell clinics onto the scene, which use more than minimally manipulated liposuctioned material to make a biological drug product via enzymatic and other steps. However, the clinics argue their products aren’t drugs and they generally do not have any FDA approval to market stem cells. Nonetheless such offerings are being sold at hundreds of clinics around the country. How would a newly minted FDA commish Gottlieb view these clinics? Through the same lens as the autologous, homologous bone marrow-based approaches? What about the clinics using bone marrow and amniotic cells in non-homologous manners that make such products drugs? Continue reading

Perspectives on Cures Act stem cell provisions possible benefits & risks

The 21st Century Cures Act has some important provisions that would impact the stem cell and regenerative medicine field.  What is driving these efforts is a widespread sense that the status quo of regenerative medicine oversight isn’t working very well.

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I’m talking with key stakeholders and still trying to sort out my thoughts on the stem cell provisions in Cures. What would it mean? Cures’ language on stem cells is nuanced and its provisions also are not so black and white as REGROW was in my view.

You can see my interview with ARM’s Executive Director Michael Werner on Cures here. ARM supports Cures. ISSCR issued a statement this morning on Cures, which is upbeat but stresses the importance of data. The statement is not a clear thumbs up or down. Earlier this year, both ARM and ISSCR opposed REGROW.

Overall, there are both potential risks and benefits to Cures’ stem cell provisions, which I discuss below. Note that this post is focused primarily on the stem cell-related provisions of Cures. There is ambiguity in terms of how Cures will affect NIH overall or have broader outcomes for the life sciences.

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Chat with Michael Werner of ARM on Cures Act regenerative medicine provisions

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Michael Werner, Executive Director of ARM

One of the hottest topics in the world of stem cells this year has been the REGROW ACT and at a larger level the movement for changes in FDA oversight of investigational regenerative medicine therapies (see my past posts on it here), so the related provisions in the 21st Century Cures Act are stirring much discussion today. The bill is called Cures for short and you can read the latest draft here.

Cures may get a vote in Congress as early as tomorrow so this is a big week for the stem cell field and the life science more generally in the U.S. See sections 3033-3036 of the bill as those are on regenerative medicine.

I’m reaching out to a number of stakeholders for their perspectives. Earlier today I interviewed Michael Werner (MW), the Executive Director of the Alliance for Regenerative Medicine (ARM) on Cures’ potential impact on the stem cell field and I have posted that interview below.

Note that ARM opposed REGROW, but supports Cures. I will post my own perspectives on the potential risks and benefits of Cures for the stem cell field and patients in a separate piece most likely later today.

What are the key reasons that ARM supports the Cures Act regenerative medicine provisions? 

MW: Four things come to mind: first, there has been a lot of talk about Japan and other countries that have taken steps to support this field and now with Cures, the United States does, too. It sends a clear signal to researchers and commercial developers that regenerative medicine is a critical technology that will be supported. Second, it optimizes the pathway without reducing FDA standards or authority. Third, it also provides for resources and flexibility in this area. Fourth, the inclusion of the standards section directing the FDA to work with stakeholders is very important. The lack of standards has been identified as an obstacle by all key stakeholders.

Will there be effects on IND/BLA requirements from Cures?

MW: I don’t think this legislation would change those specifically. The issue is to make sure that all stakeholders work together on standards development and that the FDA is part of the process. Cures does that.

What about Cures’ pre-approval (meaning the definition of an “advanced regenerative therapy”) versus post-approval requirements?

MW: I think that FDA will be comfortable with the scientific basis of whether something meets the definition of an advanced regenerative therapy. Also, the patient’s condition has to be serious or life-threatening. It was written pretty carefully. 

What does “real-world evidence” mean and is the FDA on board with that?

MW: It means using sources like patient registries and other data collected outside the formal clinical trial process. ARM had a series of conversations with FDA about the use of real world evidence and when it makes sense to include it as part of the review process. If Cures passes, the agency still has to approve the use of real world evidence in specific circumstances and it can say “yes” or “no.”

Do you think it’ll pass? Obama sign it?

MW: I think it’ll pass, and I believe if it does, that President Obama will sign it.