Big change for stem cell field with FDA quickly issuing RMATs

The 21st Century Cures Act has some important regenerative medicine language in it. One part of that was attempting to accelerate FDA review of promising investigation regenerative medicine therapies. The mechanism for this was a new designation called Regenerative Advanced Therapy, now renamed Regenerative Medicine Advanced Therapy (RMAT) Designation.

I don’t think anyone was sure how this would play out in terms of how quickly the FDA would give RMAT designations and to how many investigational products. Already it’s clear the FDA seems to be embracing the spirit of the Cures provisions as it has given out quite a few FDA granted RMAT designations and done so quickly.

The first that I could see was given to Humacyte, which has an artificial vessel research program (see image). The artificial vessels become colonized with endogenous stem cells after implantation.Humacyte

Keep in mind that RMAT designation does not equal FDA-approval overall, but it should mean the investigational therapy has solid data behind it and is promising, together equaling a faster FDA review and then potentially in the future approval should future data be strong. If some of the RMAT therapies are ultimately proven to be safe and effective, and via RMAT they were able to get to patients and help them more quickly, with few failures amongst the RMAT group, then the RMAT regulatory experiment will be proven a big success.

Here are the approved RMATs I could find so far:

  • Humacyte (Vascular Access for Hemodialysis)
  • Enzyvant (DiGeorge syndrome)
  • jCyte (Retinitis Pigmentosa)

There may be more already given, but not yet in the public domain. If you know of others please comment on the post to let us know and I’ll add them.

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.

Stem cell good news: CIRM funds new cutting edge studies

CIRM announced recently the funding of a number of exciting new studies.

ViaCyte received additional funding to support its development of its hESC-based pancreatic progenitor cell product PEC-Direct clinic trials. This work is very promising. CIRM also funded additional diabetes-related research by Humacyte on engineering blood vessels for use in dialysis, which is very creative.

VC-01 post-implant final

VC-01 post-implant

I was happy to see that my colleague here at UC Davis School of Medicine, Professor David Segal, received funding for a cutting edge grant on using gene editing for Angolan Syndrome. The grant is entitled, “MSC delivery of an artificial transcription factor to the brain as a treatment for Angelman Syndrome”.

This funding along with a new grant for Jeanne Loring on stem cells for Parkinson’s came via CIRM’s new basic biology type of funding mechanism. A number of other cool projects got funded via this RFA including one by David Schaeffer at Berkeley on stem cell-produced oligodendrocyte precursor cells to treat neurological injury.

This all is very good news for the stem cell field.