When I first learned about the multi-$10 million cord cell clinic deal between Duke and Cryo-Cell I couldn’t believe what I was reading.
Duke’s involved in this?
The problem: marketing unproven cells for kids
Yes, this wasn’t some stem cell clinic operating out of a strip mall seeking to make big money off of injecting kids with unproven stuff. Duke and the well-known cord blood biotech plan to try to make huge revenue by infusing perhaps thousands of vulnerable children with unproven cord blood cells.
That doesn’t seem right to me. It also doesn’t seem so different than some of the seriously problematic stem cell clinics.
Duke & Cryo-Cell using vulnerable kids
My first reaction back then when I didn’t even know about the $10s of millions involved in the deal was that this was likely unethical. When I read the SEC records of the company and saw the big money that was central to the deal I was even more concerned.
I’ve written extensively about this specific dicey deal to infuse autistic kids and other children with unproven cord cells. In my most recent piece I called on the FDA to freeze the Duke expanded access program or EAP that makes this controversial commercial deal possible. EAPs are supposed to be about helping terminally or otherwise seriously ill people get access to a chance for hope via a promising but not yet proven therapy. Also, EAPs are not supposed to be commercial in nature. Duke’s deal doesn’t seem to fit with an EAP on both of these levels.
The FDA approves and then oversees EAPs. The more I learned about this largely EAP-based deal with Cryo-Cell the more I thought that this couldn’t have made it past the FDA, but at some point some version of at least the EAP did.
How is that possible? Was politics involved? We need to learn much more.
Vice digs into the big money deal
There’s a new piece out in Vice by journalist Anna Merlan that helps provide more info and perspectives.
It sheds fresh light on this troubling Duke cord blood for autism program that has teamed up with Cryo-Cell. It is run by Professor Joanne Kurtzberg at Duke. I’m very glad to see more attention brought to this situation and highly recommend the piece.
I especially like the many voices that Anna brought into her story.
Alycia Halladay is the chief science officer at the Autism Science Foundation, which seeks to guide families into safe, evidence-based treatments for autism. “While stem cell therapies as medical intervention for the ASD are currently being rigorously studied at Duke, it is still too early to say they actually help those on the spectrum,” she told Motherboard. “Making the move at this time to sell this therapy to families across the world is irresponsible and dangerous. It shocks and surprises me that Duke University, an institution with a stellar academic reputation, would enter into an agreement to sell intellectual property for stem cells in autism, especially since Duke has enormous financial incentive to make this profitable for Cryo-Cell.”
Anne Borden King, who is Chair of the Campaign Against Phony Autism Cures had this to say:
“When people think of pseudoscience, they tend to think of things like a cheesy salesman selling fake pills online,” she said. “But in my work, I see quite a few examples of autism scammers hiding behind university credentials, building hype through a university. This all has a broader impact on the credibility of our universities, which are supposed to be grounded in science. Especially at this time, when we’re fighting a pandemic and we need clear boundaries around science versus pseudoscience, the impact of projects like this just really ripples out.”
The Vice story also quotes professors Leigh Turner and Jeremy Snyder, who have published important work in this area. They cited numerous issues with the Duke and Cryo-Cell effort.
Kurtzberg quotes
Anna’s story in Vice also has several quotes from Dr. Kurtzberg that are notable. In the team’s newest approach they are using cord blood monocytes to try to treat cerebral palsy and autism. As to the former, Kurtzberg invokes an unproven monocyte inflammation hypothesis:
“In email responses provided by Duke, Kurtzberg told Motherboard that monocytes “can modulate inflammation, especially in the brain. In cerebral palsy, these cells promote repair of myelin—particularly in the motor tracks, which is often damaged during injuries. We have published several papers regarding this, noting the unique properties of monocytes in cord blood.”
That seems very speculative to me. I believe all their data on monocytes is only in rodents or cell culture too. Not humans.
And she then talks about autism:
“Autism, Kurtzberg added, “is more complicated because there are multiple etiologies causing this condition. In some instances, there is inflammation of the brain, and cord blood tissue appears to calm down that inflammation in animals and lab models. We are exploring whether cells in cord blood or in cord tissue, we’re not sure which, has the ability in certain patients to calm down that inflammation and improve symptoms.”
This second quote might seem reasonable at first on its own because it suggests a real clinical trial to test whether cord cells help some autistic kids and appropriately mentions the uncertainties and complexities here, but again Duke and Cryo-Cell are essentially selling this totally unproven offering for $15,000 in parallel to doing trials. Such trials may ultimately show this approach is ineffective or even unsafe in some ways. Cryo-Cell’s SEC filings describe the anticipated income from charging families as projected revenue so I don’t really see this as patient-funded research.
Weak and negative data
What do the existing data say?
As Anna points out in her Vice story and as I have written several times, one of the biggest problems for Duke and Cryo-Cell is the weak or even discouraging clinical trial data they are standing on with this effort. Even their own trial data is largely disappointing about the utility of using cord blood for autism and other conditions.
Unfortunately for the kids and families involved, the trials don’t even ever have to be effective for the kids or even a success at ever getting an FDA approved product for Duke and Cryo-Cell to be raking in big bucks. Even if the trials flounder and keep finding largely negative or inconclusive results, which is not that unlikely, the university and biotech will still have generated possibly $10s of millions in revenue for themselves from the families via the infusion clinics. At least that’s my reading of their deal in the SEC document and other information I’ve seen.
Duke, Cryo-Cell and the FDA
Looking to the future, for Duke officials it seems the question is going to be whether the prospect of possibly tens of millions of dollars will make it worth continuing what seems to me to be a potentially unethical endeavor with Cryo-Cell to open infusion clinics based on weak or even negative data. Duke has already been benefiting from the millions from the Marcus Foundation as well as the biotech deal. It may be hard for an institution to turn its back on such huge money. I’d say sometimes you’ve got to take the difficult but upstanding path.
However, in a sense it’s not really up to Duke.
As I’ve written before, the FDA can and should stop this now by putting a hold on the program. Then the agency should re-evaluate the EAP as well as the direction it’s headed commercially. I hope the agency will err on the side of caution, particularly because we are talking about possibly thousands of children here and their families.
I’ll also say this again — the infusion clinic plan doesn’t seem so different than what some of the unproven stem cell clinics are doing. The FDA is very vocal about those unproven stem cell clinics and has taken major action recently in that space.
The unproven Cryo-Cell cell infusion clinic is set to open in just months so the agency needs to be quick about this.
From Duke’s statement in the Vice article:
“This licensing agreement does not grant Cryo-Cell the use of Duke’s EAP for the treatment of patients at Cryo-Cell, but will allow Cryo-Cell to develop its own cell therapy program.”
Cryo-cell must file their own IND application with FDA. What the agreement will do I believe is to provide Cryo-cell with a right of reference to Duke’s preclinical IND work, and so save Cryo-cell time and money. While Cryo-cell licensed the manufacturing information, I believe they must still validate their product GMPs at their own facility in the IND application. Since the company has never filed an IND (please correct me), it may be more expensive and time consuming than expected.
If and when FDA accepts their IND, it’s hard to imagine FDA would green light an EAP. It would be foolish for the company to focus on this since data collected is unlikely to support a marketing application. But of course nobody knows the mind of FDA 🙂
As for the EAP fee, each applicant must determine their own based on FDA guidance. I would be surprised if Cryo-cell’s fee was the same as Duke since the infusion is given in the Rainbow day hospital and the price reflects this.
The agreement with Duke is here:
https://www.sec.gov/Archives/edgar/data/862692/000119312520166773/d943128dex101.htm
Under Article 1 Definitions it states
“1.1 “EXCLUDED FIELDS OF USE” means autologous specific therapeutics for autism, cerebral palsy and stroke.”
I believe Duke’s trial(s) of cord blood in kids with CP involved autologous cord blood, so Cryo-cell would be starting with phase 1 if they decide to pursue this indication with allogeneic cord blood.
@Liz,
Thanks for your comment.
I’m not sure what’s going to happen. All I’ve seen suggests Cryo-Cell’s clinic is intended to open in 3 months or so, which is too soon to get their own IND or EAP I think.
Hi Paul, Any comment on this recent article from Frances Verter on “Parent’s Guide to Cord Blood Foundation”?
https://parentsguidecordblood.org/en/news/parents-guide-duke-expanded-access-program-cord-blood-neurodevelopmental-disorders
Yes, I saw that. I’m thinking most likely to write up a reply to it to post here on The Niche.
A few brief thoughts. Fran is knowledgable, a good writer, and cares a lot about this topic, but we see things very differently. In my view she’s wrongly equating the Duke/Cryo-Cell research infusions with an actual treatment and arguing that big demand from parents should justify opening an unproven clinic even if profit is part of the motivation. More to come.
I could be as simple as Cryo-Cell makes their money storing cord blood. If they start treating autistic kids, the word will get out into the community and more parents will store cord blood with them. If the treatment gets approved in the future, they have the rights to it and will make a ton.
I still don’t understand why giving someone an IV of cord blood costs $15,000!! Anyone have an explanation for that?
It does seem like a lot. I believe for compassionate use programs the FDA has to approve the charging and I thought, but am not sure, that it had to be entirely just the cost of the procedure so no profit allowed. However, all of these things are confidential so the breakdown of what goes into the $15K price tag may never be known.
At some level it’s puzzling why Cryo-Cell would be so enthusiastic about all this possible revenue via the Duke EAP if all of it just goes to the cost of the procedure itself in every case. Tons of revenue with no profit isn’t a great corporate goal. Perhaps the idea is that down the road they’ll be able to profit if they get full FDA approval? That’s a big if.
Or is there some profit built into the $15K price tag somehow?
I’m not a financial expert so just from the Cryo-Cell SEC filings I’m not clear on how this all works with Duke and company potentially exchanging all these millions or tens of millions of dollars, in some sense indirectly from the families who go to the infusion clinics, if all of the infusion money is just going to the cost of the procedure. Maybe someone else can dig into it who knows how such deals work. I’m probably missing something.
Excellent response. I couldn’t agree more.
Paul, your criticisms of Duke are piled high with innuendo- lacking facts. Worse than that, it displays your lack of understanding of how academic trials get funded and how academic clinical trials are commercialized. Where’s the broader regulatory and commercialization context? One might ask, do you have a short position with Cryo-Cell? Is that why you are soliciting whistleblowers? I don’t believe that at all, but those outlandish attacks of yours might lead others to speculate your own motives. Seriously Paul, doesn’t your own institution, UC Davis license its IP? Isn’t there a tech transfer office? Do UC Davis researchers sometimes take positions in private companies or join industry advisory boards? Of course! Isn’t that the way the world turns? But your allegations, without facts, are nothing but speculation. Further, your presumption that the activities of Duke are unethical- just sad. Damaging reputations. You have earned your powerful voice in the field. Respectfully, your war on Duke, et al., is not your best work.
Bernie,
Your comment is a kind of personal attack, but I’ll post it anyway in the spirit of dialogue. I’m also open to criticism of what I write and say. In this case I think your claims in this comment are incorrect.
Of course, commercialization is important for translation of discoveries from bench to beside and biotechs are often vital partners to academics. UC Davis has a robust clinical trials program that to my knowledge is characterized by a careful adherence to ethical standards. I’m especially proud of the scientists working in our stem cell and cancer clinical research programs.
What is going on with Duke and Cryo-Cell to open a kids infusion clinic and charge for access is vastly different and in my view inappropriate on several levels.
To the best of my knowledge, the facts are that they are prematurely commercializing an unproven product to generate revenue via a compassionate use program. Cryo-Cell’s own SEC documents and a video presentation by the CEO show that they view this as a huge new source of revenue for them.
Duke also has received and may receive millions or tens of millions more in the future as well from the deal. For this reason I’d say this is not patient-funded research. I’m not really sure how to classify it. Dr. K is a leader at Cryo-Cell as well as running the Duke program so I believe she’s responsible in some ways for what’s going on.
Bernie, you’re not a scientist, but looking at the actual data as a stem cell biologist makes me conclude that what they are infusing just isn’t ready to be used in children clinically and is not appropriate for an EAP let alone a large-scale infusion clinic as they plan.
They are still at the hypothesis and discovery stage and have regularly changed course over the past several years in terms of rationales, but now they are infusing kids anyway and charging for it? They plan to do a lot more of that starting next year? Again, to me that seems to be discordant with industry and academic standards.
Following this field for many years I only recall few examples of universities charging for large-scale access to still experimental therapies like this and they were problematic. Northwestern’s HSCT autoimmune program, now closed, comes to mind.
Finally, as you have disclosed in the past, your organization has received funding from the Marcus Foundation, a backer of the Duke/Cryo-Cell effort, which I believe is an important context for readers to know.
Great post!!