Duke & Cryo-Cell plan big clinic for unproven infusions of kids

Professor Joanne Kurtzberg’s clinical work at the Duke Autism Center on umbilical cord blood for autism and cerebral palsy (CP) involves a partnership with a publicly-traded cord blood banking firm called Cryo-Cell. Kurtzberg is also the Medical Director at the firm. In addition they have intellectual property in this area. The Duke team’s efforts, including those done outside of clinical trials and that require family payments, have been concerning to me for some time.

Now the partnership seems to be heading in a more worrisome direction. Their plans remind me of unproven stem cell clinics in several ways.

I believe the FDA needs to take a close look at what’s going on and maybe put a hold on the expansion plans.

What’s in this article

Kurtzberg cord blood program issues | Disappointing trial data | Past infusions outside of clinical trials via EAP | Stepping on the gas for off-study infusions | Explore, test, administer? | Concerning marketing | Fees adding up to $33 million? | Moving into the realm of unproven stem cell clinics? | EAP and FDA considerations | Where’s the data needed for this type of EAP? | Precedent of Northwestern pay-for-play program isn’t reassuring | The FDA should step in here | References

Quick Article Summary and Claim Review. Duke and Cryo-Cell claim that cord blood is promising enough for autism and other pediatric neurological disorders to inject hundreds or thousands of kids outside of clinical trials. They also require payment for this. However, clinical trials have not produced data to support this claim. The most rigorous study to date by Duke itself suggests no clear benefit. Other trial data also are not supportive of this claim. There are risks too and the procedures are expensive. Overall, this claim is highly questionable. You should consult your child’s pediatrician.

Ongoing Kurtzberg cord blood program concerns

For background, over the past few years I’ve been skeptical of the Kurtzberg team’s clinical research on autism and CP. In my view, there have been three main issues of concern that remain ongoing. The new development just multiplies the concerns.

• First, trial data just aren’t there to support their hypotheses. Both their own data and that from other groups are generally discouraging. There is just no strong evidence that cord cells can help autism or CP in a significant, consistent way. That could change in coming years, but in my view the odds are against it. Data are sometimes being analyzed in a post-hoc way seemingly to try to squeeze out some signs of benefit for some kids. I think this is giving families false hope.
• The second issue is injecting kids off-study with unproven cord materials and charging. As their clinical trials have been ongoing, Kurtzberg’s team has taken a shortcut too. In parallel the team has already been injecting hundreds of children via an expanded access program (EAP) with unproven cord material. And they are requiring families to make big payments for this unproven offering. That’s an ethically dicey combination in my view.
• Thirdly, there are reverberations with a Panama stem cell clinic. In my view her team seems to have a kind of symbiosis, perhaps unintentional, with a for-profit Panama stem cell clinic. It’s called The Stem Cell Institute. This Panama clinic sells unproven cord cell-based injections for autism and many other unrelated conditions. The clinic leader may have had a role in Kurtzberg’s team getting tens of millions of dollars from something called the Marcus Foundation. Families often discuss and link the Duke program and the Panama clinic together in their thinking.

Consistently disappointing data

What about the data?

The data say there’s little reason for optimism that Duke’s cord blood infusions can help children with CP or autism. However, the team keeps up the cheer.

I’ve written about their characterization of their own rigorous clinical trial on cord blood for autism, which showed no clear benefit on primary endpoints, as “encouraging” when they looked after the fact at only a subset of data for only certain kids. This is called post-hoc analysis.

I thought that the team also had mostly discouraging data on cord blood for cerebral palsy.

And it’s not just their data. For example, a clinical trial by Sutter here in Sacramento also did not find any statistically meaningful indications of benefits from cord stem cells for autism in any endpoints. That team mentioned possible hints here or there of something, but were appropriately cautious.

Past infusions via EAP

What’s gotten less attention than the Duke clinical trial work is that in parallel they have continued to offer large numbers of families the option to get their kids infused with cord blood cells “off-study” via an expanded access program or EAP. My understanding is that nearly 500 children have been infused with unproven cord cells already.

And all these families coming to Duke are having to pay somehow for access to scientifically unproven cord blood cells for autism or CP.

It might be technically permissible to do all these infusions outside of a clinical trial if you get the OK from the FDA. The agency sometimes even permits requiring fees.

But when is the last time the FDA took a close look at what’s going on there these days and the future plans? Is there actually enough good data to support this EAP even in its current form? I’m skeptical.

The charging aspect especially seems odd when Kurtzberg has received potentially those tens of millions of dollars from the Marcus Foundation for the work.

Here’s the actual Clinicaltrials.gov listing for this EAP. It doesn’t give much in the way of details.

Stepping on the gas for unproven infusions

Now a new development makes me more concerned than ever about Kurtzberg’s and Cryo-Cell’s efforts in this area.

It seems they plan to inject a vastly increased number of children at one or more of their own new stem cell clinics they are setting up. Again, these infusions are not well-founded medically or scientifically.

In a new item “Infusion Clinic Expected to Open by January 2022” Cryo-Cell describes expanding infusions of unproven cord products for kids with various conditions including autism and CP. It begins (emphasis theirs):

Recently, Cryo-Cell entered into an exclusive license agreement with Duke University, which grants us the rights to proprietary processes and regulatory data related to cord blood and cord tissue developed at Duke. This agreement also makes Cryo-Cell the only cord blood bank with the right to offer treatments to children at its own infusion clinic under Duke’s FDA-approved Investigational New Drug Application (IND). Cryo-Cell expects to open its first clinic by January 2022.

While the Cryo-Cell post references an FDA cleared IND, the treatments themselves being marketed here are not FDA-approved as drugs.

Their article also includes a form for parents to fill out. That seems like a classic marketing approach to get more clients. After all, Cryo-Cell is a for-profit firm, but I didn’t think it was kosher to financially gain from an EAP. Is that possibly happening here? It’s hard to say. I’ve got more on the financials below.

Explore, test, and administer?

On a website Parent’s Guide to Cord Blood Foundation another parallel new item adds more red flags. It is in part about the same development mentioned on the Cryo-Cell site. The piece first discusses the agreement between the university and the company.

“Under this agreement, Cryo-Cell plans to explore, test, and administer umbilical blood and cord tissue derived cell treatments to patients with conditions for which there are limited FDA-approved therapies. Currently there are limited FDA approvals for several pediatric neurological conditions, such as cerebral palsy and autism, and there is the potential to eventually include stroke and other adult diagnoses. These treatments utilize the unique immunomodulatory and regenerative properties derived from cord blood and cord tissue cells.”

Explore, test, and administer?

That sounds more like what should be done in pre-clinical and clinical trial research.

How is that allowed for an unapproved cellular drug product outside of the clinical trial process? And to require families pay?

You might say, “what about those mentioned unique immunomodulatory and regenerative properties derived from cord blood and cord tissue cells?” These “properties” are actually just theoretical in terms of having a benefit for autism.

Concerning marketing

The article goes on to describe “extended benefits for patients”. See screenshot above. But clinical trial data do not clearly point to efficacy.

They also claim that this will revolutionize treatment outcomes. That sounds more like an unproven stem cell clinic statement or advertisement.

Note that Duke has a new clinical trial to test cord stem cells for autism, whereas before as best as I can tell they used whole cord blood in their trial. The Parents Guide article also is too upbeat about this new trial and assumes this experimental offering will become available through the EAP program as well:

“Duke University is also conducting a clinical trial using human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with Autism Spectrum Disorder5. As the trial progresses, we anticipate this treatment becoming eligible for Expanded Access Protocol (EAP). Upon EAP approval, Cryo-Cell will become the first infusion clinic to offer this therapy to families in need.”

But shouldn’t this new “treatment” only become available if the new clinical trial produces rigorous, encouraging data on efficacy?

I guess they are just assuming the FDA will allow anything goes for their EAP no matter what the data say?

What if this supposed therapy just doesn’t work? This team seems to exclude that possibility.

Also, while cord blood products seem generally pretty safe, there are going to be some risks. Some of those risks may not yet be understood or only become apparent in the long run.

Fees possibly adding up to $33 million?

The monetary aspect to all of this is not mentioned in the new articles. It is generally a topic that Kurtzberg seems to avoid too. Even so, it’s a big deal.

The Patient’s Guide article goes on (emphasis mine):

“Since 2017, Duke’s Expanded Access Program (EAP) has enabled hundreds of families who have stored their children’s cord blood to take advantage of investigational therapies offered at The Marcus Center for Cellular Cures at Duke University. Children with various brain disorders, such as autism, apraxia, cerebral palsy, congenital hydrocephalus, hypoxic brain injury, and stroke, are eligible to participate. Dr. Joanne Kurtzberg, Director of The Marcus Center for Cellular Cures at Duke University and Cryo-Cell’s Medical Director, reported that over 400 patients had been treated as of December 2020. They also report that over 600 additional patients have been screened and another 1,600 patients are awaiting follow-up contact…Licensing of Duke’s EAP treatment protocols allows Cryo-Cell to offer children the same high-quality care they have received at Duke, but with the location shifted to one of their forthcoming infusion clinic locations.”

Those future numbers add up to 2,200 children who may go to the infusion clinics. At least that seems to be the implication of what is written there. The numbers could go much higher too if the FDA gives the OK.

Without more data, how can what is offered be described as “high-quality care”? The word “care” suggests a known benefit.

To the best of my knowledge the families here will have to pay to go to this clinic. If payments were to average $15,000 per child (which is what I’ve seen on the web consistently up until now for this EAP) and 2,200 children got infused, that’s $33 million for Duke and Cryo-Cell. 

This raises many questions.

What if a family cannot afford $15,000? Are they excluded? If so, is that ethical?

What will be the role of health insurance if any at the Cryo-Cell clinics? Apparently some insurance companies are covering this EAP, but many are not.

Does this charging benefit the team itself?

Does the Marcus Foundation get any of the money?

Leigh Turner and Jeremy Snyder have done research and published a few papers on the Duke & Stem Cell Institute issues including a recent one. I recommend their work for more background.

Moving into the realm of unproven stem cell clinics in some ways?

Readers of The Niche will know that I’ve been battling against unproven stem cell clinics for a long time. These clinic firms charge for stem cell-related offerings for many conditions although what they inject is neither proven scientifically nor approved by the FDA.

Because of what Duke and Cryo-Cell are now doing, I have had to ask myself a painful kind of question: “How is what Duke is doing here different than an unproven stem cell clinic”?

Especially with the new plan for fee-for-access Cryo-Cell stem cell clinics, this seems awfully similar on a number of levels to the unproven stem cell clinics. It is expensive, scientifically unproven and has not received final approval from the FDA.

One major difference is that Duke’s off-study administration of cord blood cells for autism or CP must have been OK’d by the FDA as an EAP.

FDA, what do you think of this now?

EAP and FDA considerations

I asked FDA legal expert Patti Zettler, an Associate Professor at Ohio State University, about this situation. As usual, she helped me understand the context here much more clearly:

“In general, expanded access is not intended as a means to commercialize unproven interventions. The more a program seems like commercializing an unproven intervention, the more questions it raises about whether it is consistent with the purpose of expanded access. Non-trial preapproval access is not, and should be used as, a means to sell or distribute unproven interventions.”

To me the Duke/Cryo-Cell plans sure seem similar to commercialization via an EAP in some ways. It’s not clear to me if Cryo-Cell, Duke, or Kurtzberg will financially benefit from the EAP or future efforts based on the EAP. It’s at least possible.

Interestingly, Patti did indicate that a large EAP for autism could be permissible in some circumstances:

“An expanded access program for a large group of patients with autism doesn’t seem to me to be necessarily out of the question. This is because expanded access can be authorized both for patients with immediately life-threatening conditions and those with serious conditions, without comparable or satisfactory treatment options. Serious conditions are defined pretty broadly and could cover many conditions. Additionally, although the overwhelming majority of the expanded access requests that FDA receives are for “individual patient” programs (covering, roughly, 1-10 patients), FDA also can authorize “treatment INDs” or “treatment protocols” for large groups of patients.”

Where are the data needed for this type of EAP?

But she raised a point about the hurdle for data needed to have such a program.

“That said, for a large treatment program, among other things, the intervention must be under investigation in clinical trials to support a marketing application for the expanded access use (or the trials must be completed and the sponsor must be actively pursuing approval), and there must be sufficient evidence of safety and effectiveness that, for a serious condition, “would ordinarily consist of data from phase 3 trials, but could consist of compelling data from completed phase 2 trials.”

See this FDA page for more info.

I don’t see how Duke’s EAP meets the data criteria outlined above. They do not have Phase 3 data and their Phase 2 data missed its primary endpoints. Patti also raised another consideration:

“Additionally, for any expanded access program, FDA must determine that the program will not interfere with the conduct of clinical trials studying the expanded access use (for example, by making it difficult or impossible to enroll patients in the trials rather than the EAP). Especially with a large program, as this one seems to be, I think it’s fair to wonder about the impact on clinical trials.”

To me it seems like recruiting hundreds or a few thousand kids with autism or CP off-study via an EAP could have a major negative impact on the ability of Duke as well as other teams to run solid clinical trials in this area.

Overall, based on an FDA resource page on expanded access program or EAP that lists criteria that EAPs must meet,  I don’t think the Duke autism/CP program passes muster as an EAP.

Precedent of Northwestern pay-for-play program isn’t reassuring

This all also reminds me of the now-shuttered stem cells for autoimmune disease program at Northwestern run by Dr. Richard Burt.

There too it seems patients had to pay for access to experimental stem cell-related infusions.

In addition, many patients were apparently “treated” off-study with stem cells and also had to pay. It seemed on some level to involve an EAP too.

The FDA should reevaluate this EAP and its plans

As compared to Duke/Cryo-Cell, one big difference is that at least Northwestern had unambiguously encouraging data on efficacy. To my knowledge Duke does not. Many of the autoimmune patients at Duke had clearly fatal or potentially fatal illnesses too.

It’s concerning that the language used by Cryo-Cell, Duke, and others to describe the cord infusions for CP and autism is way too upbeat and cheery. This borders on hype. Looking at message boards, Facebook, and elsewhere, it seems to me that parents have been led to believe that this unproven offering definitely works and is totally safe.

What about the FDA’s role here?

The FDA is going to allow groups to run EAPs for hundreds or thousands of patients and to require payment for that access even if the data are not compelling?

It seems to me that this practice risks doing a great disservice to the kids, their families, and the stem cell field. It also risks undermining the clinical trial and FDA approval system.

This “therapy” is just not ready and may never be. I hope I’m wrong, but medical science is extremely difficult. If you’re going to infuse hundreds or thousands of children with stem cells and require families to pay big bucks for it you better have amazing data to back that up. I don’t see that.

I believe the FDA should take another close look at the Duke/Cryo-Cell EAP in this case and perhaps take some action. This is especially urgent given the apparent expansion plans.

References

1. FDA resource page on expanded access program or EAP.
2. Parents Guide to Cord Blood Foundation announcement on Cryo-Cell clinics.
3. Infusion Clinic Expected to Open by January 2022 announcement on their new clinics and deal with Duke.
4. Boosted by celebrity endorsements and a controversial research program, clinics are peddling stem cell autism treatments questioned by experts, Tom Porter, Business Insider, January 2021.
5. Experts question rationale for stem cell trial for autism, Hannah Furfaro, Spectrum, July 25, 2019.
6. Should You Bank Your Baby’s Cord Blood?, Dana Najjar, New York Times, December 18, 2020.
7. Snyder-Turner paper linking Panama clinic and Duke program, Crowdfunding, stem cell interventions and autism spectrum disorder: comparing campaigns related to an international “stem cell clinic” and US academic medical center.
8. Key past Sutter trial publication on cord blood stem cells for autism.
9. Duke EAP for “brain injuries” on Clinicaltrials.gov.