You are here
Duke Removes Autism from Cord Blood Expanded Access
During the year 2022, Dr. Joanne Kurtzberg’s team at Duke University Medical Center (Duke) quietly stopped enrolling children with Autism Spectrum Disorder (ASD) into their Expanded Access protocol listed on ClinicalTrials.gov as NCT03327467. Expanded Access (also known as Compassionate Use) is a regulatory mechanism by which the FDA allows the developer of a medical therapy to make the product available to patients before it is fully approved for the market. In order to qualify for the FDA’s Expanded Access pathway, certain conditions must be met. The product must have a demonstrated safety profile, must have shown promise for efficacy in previous clinical trials, the product must continue to be in clinical trials (the EAP cannot be a substitute for trials), and the patients must suffer from a condition that is life-threatening or debilitating. The FDA regulations allow the developer of the product to charge patients for the cost of administering the product, but they cannot charge for the product itself without further regulatory approval through a mechanism called cost recovery.
Since 2017, Duke has had FDA approval for an Expanded Access program (EAP) which covers the use of autologous and sibling cord blood infusions to treat a variety of neurodevelopmental disorders in children. These include perinatal stroke, oxygen deprivation at birth (or hypoxic ischemic encephalopathy, HIE), hydrocephalus (fluid in the brain), Cerebral Palsy (CP), and also ASD. This program allows eligible children to receive an infusion of their own cord blood or cord blood from a full sibling, provided the cord blood has an adequate cell dose, is sterile, and is a close enough match (for a sibling unit). What has now changed is that at the end of 2022 Duke voluntarily removed ASD from the list of treated diagnoses. The EAP NCT03327467 is still active, but with one diagnosis removed from the list.
The primary reason that ASD was removed from the EAP is that the research team at Duke is weary of defending themselves against vitriolic attacks from a small but passionate group of opponents who imagine themselves to be defending families of children with autism. Some of these attacks have targeted members of the research team for personal harassment. The researchers want to stop having to be defensive and just focus on the research in their clinical trial pipeline. It is important to note that neither the research staff nor Duke University have a financial motive to keep the EAP going, since the income from the program simply recovered the costs associated with the treatment.
The events leading up to and following this decision have generated so much mis-information, that the remainder of this article is devoted to reviewing the history of the EAP debate and debunking false rumors.
The cord blood EAP was originally launched in October 2017. From the very beginning, Duke was charging patient families $15K to participate in this program. This charge was set based on the cost of running the program with a high standard of care at an advanced medical center. The cost recovery includes, but is not limited to: screening the patient, testing the cord blood unit, performing a history and physical the day prior to the infusion, performing the infusion in the pediatric infusion center including the supplies and pre-medications, observation by nursing and medical staff during the infusion, and follow ups that day, the next day, and weeks and months later out to 2 years post infusion, as outlined in the EAP protocol registered under the IND with the FDA.
Within the community of parents that have children on the spectrum and are considering experimental cell therapy, the EAP price was well known for years. For comparison, the most well-known commercial clinic, the Panama Stem Cell Institute, charges about $20K to give cell therapy for autism. Parents in support groups regularly discussed the trade-offs between going to a commercial clinic versus participating in the EAP. The waiting list for Duke’s EAP quickly became unmanageable. Over 17,000 families had applied by 2021, and the accepted families were waiting two years for treatment. Quite a few families bailed off the EAP waiting list and went to a commercial clinic instead, because they wanted their child to receive cell therapy at a young age.
The opposition to the EAP started in late 2021, after four years of operating in obscurity. In spring of that year, Duke had signed an exclusive license agreement with the company Cryo-Cell International (publicly traded on Nasdaq with the stock symbol CCEL). The licensing agreement would enable Cryo-Cell to offer Duke’s FDA-approved cell therapies, including the EAP, at a new infusion clinic. This would have benefited families trying to get access to the EAP therapy because the clinic would be able to treat about five times more patients per week. Of course, Cryo-Cell proceeded to promote this agreement to their investors. But as a result, a wider audience became aware that Duke was charging EAP participants $15K, and that Cryo-Cell intended to continue with that price.
The first wave of opposition to the Duke EAP for Autism came from a few professionals who work in the cell and gene therapy (CGT) field. They claimed that the price of the treatment was outrageous and that the program was taking advantage of vulnerable parents.
The second wave of opposition to the Duke EAP for Autism came when a couple of CGT professionals recruited the help of a journalist at an on-line magazine which thrives on reporting about conspiracy theories. In October 2021 the autism treatments at Duke were splashed across the media as a “big business” centered around an “unproven treatment.” This type of accusation is actually a regular occurrence in the autism arena. The nominal gold standard of autism therapy, Applied Behavioral Analysis (ABA), has also been described as a big business built on an unproven treatment. The underlying problem is that there is no proven treatment for profound autism, or else we would not be having arguments about experimental treatments.
The third wave of opposition came when the press coverage reached the community of advocates for neuro-diversity. These are organizations of adults on the ASD spectrum who argue that autism should be accepted, that they do not need to be “cured.” Their anger led to intense personal attacks on members of the Duke research group. It is sad when adults that are on the high-functioning end of the spectrum attack people who are trying to help children that fall on the low-functioning end of the spectrum. Even the acknowledgement of “high” versus “low” functioning is objectionable to this political camp. When children have profound autism, their parents worry if they will ever master enough skills to live independently once their parents are gone. Will their extended family take care of them? Will society take care of them? What is the harm in letting these families try a wide range of therapeutic options?
During the Coronavirus pandemic, all clinical trials at Duke were shut down. Trials that had started to treat children before the pandemic lost the patients that had been accrued because the children could not return for follow up testing. Duke restarted their clinical trials for neurodevelopmental disorders in 2022, sometimes with changes in protocols to accommodate more social distancing. Duke currently has three clinical trials running that treat autism with mesenchymal stromal cells from umbilical cord tissue (UC-MSC). The largest active trial is the IMPACT trial NCT04089579 which has finished recruiting 137 children and is currently in the follow up phase. The team is ready to launch a multi-center phase 3 trial of cord blood for cerebral palsy. Eventually they want to run a phase 3 trial of cord blood for autism, only selecting participants that belong to the sub-group which showed benefit in their phase 2 trial. It is possible that at some point in the future Duke will resume expanded access therapies for autism, either with cord blood or with UC-MSC.
Ironically, when Duke stopped offering the controversial cord blood EAP for ASD, it triggered a new round of media coverage which contained new speculations that are wildly inaccurate.
There has been repeated speculation in blogs that perhaps the FDA worked behind the scenes to force Duke to shut down the EAP for ASD. This rumor has been repeated on social media so many times that people who are not following the story closely only recall hearing “the FDA shut them down.” When that happens, the rumor has metastasized into fake news. For the record, the FDA has not shut down any aspect of Duke’s Expanded Access program for cord blood therapies. In early 2022, the FDA conducted an onsite audit of the EAP, which by that time had treated nearly 600 children. The inspection did not find a single 483 Observation, which is the lowest level of FDA criticism. The FDA is not allowed to comment on organizations that they regulate, but the FDA does not make observations or enforce changes behind the scenes, every action is a matter of public record. FDA citations and 483 observations are published in the Federal Register, and if the FDA issues a Warning Letter or conducts an Enforcement Action, those are published on the FDA website. There is no public record of the FDA citing the Duke program or shutting anything down, which proves it didn’t happen.
Another fanciful speculation is that, if Duke is no longer offering cord blood for ASD, this will enable their licensee Cryo-Cell to take over their autism business. That is not how FDA regulations on EAP work. The IND registered with the FDA belongs to Duke, it is not a fumbled ball that some one else can pick up and run with. While cord blood therapy for ASD was part of Duke’s EAP, Duke could allow a licensee to offer the therapy, but now that Duke has taken the diagnosis ASD off the EAP list, it cannot be offered by anyone. Parents that wanted to enroll in the EAP are not being driven to Cryo-Cell, if anything they are being driven to cell therapy clinics outside the US.
We are the first to report that there is also a financial aspect to this story. For years, Dr. Kurtzberg’s clinical trials at the Duke Marcus Center for Cellular Cures have received generous support from two philanthropists, The Robertson Foundation that was launched by Julian Robertson of the Tiger Fund, and The Marcus Foundation that was launched by Home Depot founder Bernie Marcus. This support was based on a series of personal meetings where Dr. Kurtzberg and colleagues presented their prior work and research plans to Mr. Marcus. However, Mr. Marcus is getting on in years, and his Foundation is undergoing a reorganization to a more formal management structure. A fall-out of this overhaul is that The Marcus Foundation is no longer giving grants to support research in regenerative medicine. We are aware of this because we have talked to other organizations that relied on funding from The Marcus Foundation. As a consequence, the Duke team has had some struggles to secure funding for clinical trials of cell therapy to treat neurodevelopmental disorders. This is why the Cryo-Cell 2022 annual report reveals that they stepped in to fund the completion of the IMPACT trial.
The saga of Duke’s cord blood EAP for autism is a cautionary tale on several levels. The “patient advocates” that shut down this program virtually never talk to the constituents that they claim to be protecting. It is a textbook example of paternalism in action. This Foundation has interviewed a number of parents that are active in the community that seeks cell therapy for ASD, and none of them is happy about the closure of the Duke EAP for autism.
It is probably a safe prediction that this episode will have a chilling effect on future Expanded Access programs. Back in 2021, we interviewed the CEO of WideTrial, a company that helps product developers to manage expanded access programs. His words then continue to be relevant today: “Mr. Rabourn acknowledged that cost recovery is a sensitive topic in the EAP community; when manufacturers cannot find a way to pass on costs, they respond by restricting access, and patients lose out.” If we add in fears that the program may be sabotaged by rival researchers, that the program may be targeted by a magazine that prides itself on gonzo journalism, or that medical staff may undergo stalking and harassment, then manufacturers of cell and gene therapy products have all the more reason not to open Expanded Access programs.