Wouldn’t you like to be a RAT too? Stem cell clinics apply for new FDA accelerated approval path

RAT RMAT designationAre stem cell clinics going to somehow get the FDA to approve their stem cell interventions? To get recognized as legit? It seems they are trying now more than ever.

Remember the REGROW Act that would have greatly reduced regulations on investigational stem cells and then how the 21st Century Cures Act passed with some REGROW-related provisions, but more moderate ones?

The status quo of how the FDA regulated stem cell-based regenerative medicine therapies wasn’t working so great in past years so some reforms were (and still are) needed, but the key was hitting the “Goldilocks” sweet spot of just the right amount of regulatory change.

I was worried about REGROW in particular because I viewed it as having overshot by a mile by going for too much reduction in oversight (particularly in its original language, although it moderated somewhat over time) and I had mixed feelings on Cures, but it was at least relatively more balanced. Cures passed, was signed by Obama, and is now law. One of its main provisions on stem cells is so-called Regenerative Advanced Therapy (RAT, an unfortunate acronym choice that it seems the FDA wants to change to RMAT) designation that could speed up vetting of stem cell therapies.

My concerns about the legislative efforts were mainly stemming from the possibility that stem cell clinics would try to take advantage of the less stringent regulations. Could they get their interventions to be designated as RATs? Could some of the clinics get FDA approval?

Now some of the clinics are trying to make that a reality.

I’m hearing from multiple sources that a number of stem cell businesses running clinics have already applied to the FDA for RAT/RMAT designation that puts therapies automatically on the accelerated pathway. Most of these businesses have not publicly announced their applications, but US Stem Cell, Inc., a publicly-traded stem cell clinic company disclosed that it has applied for RAT status. You might recall this businesses as it was associated with the blinding of three of its patients. I’m hearing that other businesses are already applying for RAT too. US Stem Cell wrote:

“Following the passing of the 21st Century Cures Act, U.S. Stem Cell, Inc. has applied to the FDA for RAT Designation. We have recently heard from the FDA, who has requested additional information regarding the MARVEL Phase II/III trial. We have provided all requested information to the FDA and are hopeful that the FDA will continue their expeditious review of our MyoCell product. Thanks to the REGROW component of the Cures Act, the FDA will grant RAT designation for a regenerative medicine therapy that is intended to treat, modify, reverse, or cure a serious or life-threatening disease and demonstrates preliminary clinical evidence that the product has the potential to address unmet medical needs for a disease. We believe that our MyoCell product meets these requirements, as we have demonstrated clinical efficacy in both preclinical and clinical studies…”

Presumably, some of those working on investigational stem cell therapies from non-clinics are going for RAT designation too and some of those are probably not going to get approved. On the other hand, some stem cell clinic and non-clinic applications to the FDA may get the RAT stamp of approval.

Overall, how will the FDA decide what to approve as a RAT and what to reject as not a RAT? How effective will the FDA be able to be on vetting the host of RAT applications it is getting?

Showing how fast this could all happen, the FDA has already granted the now-re-named RMAT designation to some companies including Humacyte, which is in part funded by CIRM and this RMAT designation seems like a positive move.

Hold on to your hat (or chair, or pet rat, or whatever) as we will now all witness a high stakes regulatory experiment unfold in front of us in the coming months and years due to Cures. The outcome is likely to be mixed overall, but we can hope it’ll be on the whole a positive for the field and for patients. There’s no crystal ball on this though.

REGROW Act 2.0 still no-go with big risks to patients & field

Mark Kirk REGROW ActThe REGROW Act is a bill that seeks to lessen the regulatory burden to accelerate getting stem cells to patients more quickly, but it over-reaches so much that it would almost certainly do harm to patients and maybe to the stem cell field as a whole.

The REGROW Act, which is sponsored by Senator Mark Kirk of Illinois, has had several incarnations, but the latest new one reflects some big changes so I’m going to call it REGROW 2.0.

A source provided me with a copy of REGROW 2.0 and it is surprising in a number of ways. Unfortunately the bottom line is that it is still a no-go because it would be so risky.

The original REGROW would have forced a conditional approval system on the FDA whereby still experimental stem cells could be given to patients with little data supporting this use.

REGROW 2.0 has dropped the extreme conditional approval so that seems like a good thing. Instead 2.0 focuses on accelerating approval, which on the surface also seems like it could be a positive thing. However, the devil is in the details.

Too broad on cell product type? The new version of the bill drops all requirements on the types of cells that would qualify including the previous filters for genetically modified cells. So anything goes for stem cell types in REGROW 2.0.

Too weak on medical conditions? The new version of the bill also would weaken in a really big way the standard requirements for accelerated approval for experimental stem cell products by the FDA. No longer would the patient need to be facing a very serious condition with unmet need such as a fatal illness, but now instead the acceleration could be used for many things that fit into the broader category it stipulates:

“the treatment of a serious condition for which the product is approved under this subsection may include a chronic, persistent, or recurring condition that affects day-to-day functioning without taking into account the availability or lack of alternative treatments.”

Devices mess. This could mean almost anything so REGROW 2.0 would put a big old loop-hole in there. REGROW 2.0 also still seems problematic related to stem cell devices as it is weak on the rules required for determining what can or cannot be used.

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Is REGROW Act anti-embryo research? Pluripotent stem cells excluded

REGROW ActThe REGROW Act has attracted both support and criticism, including on this blog, for the changes it would mandate in the way the FDA regulates stem cell products. More specifically it would greatly reduce regulation of experimental stem cell products. I believe that would be dangerous to patients and to the stem cell field more generally.

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Alliance for Regenerative Medicine (ARM) Opposes REGROW Act, Risks to Patients Cited

The biggest debate today in the stem cell world is over how much regulation is needed for new, investigational stem cell therapies that are not as yet approved.

Sometimes it feels very lonely being out there publicly advocating for appropriately thorough regulation of stem cell therapies and at times I get a lot of heat for that, especially from stem cell clinics. For instance, I am publicly opposed to the REGROW Act, a piece of legislation that would dangerously weaken oversight of experimental stem cell therapies. Still, I have not yet seen a statement from major stem cell organizations on these issues. It was therefore a great boost to hear just now that the top stem cell biotech industry organization, The Alliance for Regenerative Medicine (ARM), has issued a statement firmly opposing the REGROW Act.

Alliance for Regenerative Medicine

I want to send kudos to ARM and its more than 250 members.

For years in this debate there was a bright line between the academics as well as mainstream organizations in the stem cell arena (together supporting the need for rigorous science-based stem cell medicine and for the FDA, even if some reforms are needed) versus the dubious stem cell clinics out to make a quick buck and wanting as little regulation as possible.

However, in the past year we’ve seen a troubling seismic shift such that some academics and others who used to support the FDA have begun arguing for dramatically less regulation of experimental stem cell treatments. For more background on these pushes for stem cell deregulation, please see my past posts on the Bipartisan Policy Commission (BPC) report that proposed extreme measures such as conditional approval of experimental stem cell interventions, charging patients to be experimented upon, and eliminating Phase III trials in some cases and also see my post opposing the REGROW Act.

It is a big, positive decision for ARM to oppose the REGROW Act, and I’m encouraged to see that I’m not alone in opposing this overreaching legislation. The reasons for ARM’s opposition and my own rationales for being against the bill substantially overlap. We both focus on the dangers posed to patients by inappropriately extreme deregulation. I can’t speak for ARM, but my impression is that they like many of us support some changes in how stem cell therapies are regulated. Perhaps there is hope that the REGROW Act could reemerge in a new incarnation in the future that is more balanced and would chart a prudent path forward.

I’ve pasted ARM’s statement on the REGROW Act below:

“The Alliance for Regenerative Medicine is appreciative of Senator Kirk’s longtime support of the regenerative medicine sector and his belief in the transformative durable treatments and potential cures this field holds for patients. Our organization is committed to our continued cooperation with Senator Kirk and his staff to advance policies supportive of this sector and expediting potentially life-saving cell therapies, gene therapies and other regenerative medicine products. 

However, ARM cannot support the REGROW Act. We continue to believe the proposal does not contain critical statutory protections for patients. We look forward to a continuing dialogue with the sponsors of REGROW Act as well as other stakeholders to create alternative approaches to ensure access to safe and effective regenerative medicine therapies without putting patients at risk, disadvantaging American therapeutic developers and potentially damaging a very promising field of medicine. 

Note that ARM leaders Michael Werner and Edward Lanphier seem to be the point people on the REGROW issue.

REGROW Act is Attack on Science-Based Stem Cell Trial Oversight

REGROW ActSenators Mark Kirk, Joe Manchin, and Susan Collins have proposed new legislation in the form of the REGROW Act that would substantially interfere with the FDA’s ability to properly regulate the development of new stem cell and regenerative medicine therapies based on hard science.

The REGROW Act would force the FDA to allow rushed introduction of experimental stem cell interventions into patients even if the science did not support that these were safe or effective at that time.

From the Kirk press release:

“Unfortunately the Food and Drug Administration (FDA) has identified the current lack of regulatory standards in this area of medicine as an impediment to treatment development. Countries like Japan and England are outpacing the U.S. in regenerative medicine therapy development due to new regulatory policies that the U.S. has yet to mirror.

S. 2689 will allow the United States to regain prominence in the field of regenerative medicine science and bring therapies quickly to the patients that need it most.”

This libertarian agenda fits with the recent BPC report that overreaches on FDA deregulation. See my take on the BPC report here.

You can also see a nationalistic agenda evident in the language that is not scientific. Just because some authorities in Japan have chosen to dramatically weaken regulation of stem cell therapies there and made other questionable decisions such as more widely allowing charging of patients to be in stem cell clinical trials, doesn’t mean the U.S. should follow the same somewhat reckless path.

These practices are highly questionable from a bioethics perspective and also from a simple common sense view that rushing ahead too fast can actually slow things down by leading to catastrophic patient outcomes. The Jesse Gelsinger case with gene therapy comes to mind and its interesting that some advocate a race car mentality for use of CRISPR in humans too.

My understanding is that the dubious stem cell clinic lobbying force is happy with the REGROW bill as it would shift the regulatory framework toward their philosophy even if they don’t get everything they want. REGROW proponents want to rocket forward with stem cells into patients by eliminating Phase III trials and establishing a risky conditional approval paradigm. I haven’t seen any evidence that Phase III clinical trials for stem cells are unnecessary nor that the conditional approval paradigm would be safe.

The REGROW Act summary page is here and the full text of the bill is here. Fortunately analysts predict only a 4% chance of passage of this dangerous bill.