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Expanded Access to Advanced Cell Therapies

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Guest Author:  Frances Verter, PhD, Parents’ Guide to Cord Blood Foundation


Thank you to Ax-S Pharma for the invitation to submit a contribution to your blog. My name is Frances Verter, and I am a founder of two organizations in the cell therapy space: the 501c3 non-profit Parent’s Guide to Cord Blood Foundation, and its for-profit subsidiary My goal in this blog is to inform readers who are insiders of the Expanded Access space about the latest news regarding Expanded Access in the arena of advanced cell therapy.

The phrase “advanced cell therapy” has a specific regulatory meaning. Both the FDA and the EMA consider a cell therapy to be advanced if the cells are more than minimally manipulated and/or if their action is not homologous. Advanced cell therapies are regulated as biologic drugs. During the time frame from the beginning of 2017 through mid-2021, the FDA has given 15 Expanded Access approvals to deliver advanced cell therapies to intermediate and large size groups of patients1. This is a tiny number compared to the total of 913 clinical trials registered during that time frame to deliver advanced cell therapies in the United States1.

A classic example of an advanced cell therapy that has received a lot of media coverage are the CAR-T therapies in which a patient’s own T-cells are genetically modified to recognize and kill cancer cells. These personalized cancer treatments offer improved survival with lower toxicity than conventional therapies2. Our database from 2017 to mid-2021 includes six Expanded Access approvals for CAR-T therapies1. But despite the excitement that CAR-T therapies have generated in the entire oncology community, the number of cancer patients that are eligible for this novel therapy is still small.  At present, less than 5% of new cancer diagnoses can be treated with the approved CAR-T products that target the CD19 marker3.  It is hoped that eventually CAR-T therapy will be applied to a large fraction of patients with severe hematologic cancers, which would be approximately 1 in 200 people in the United States over the course of their lifetime, or about 18 thousand cancer patients per year4,5.

Meanwhile, another advanced cell therapy that treats pediatric neurodevelopmental disorders is already swamped with patient requests for Expanded Access.  Duke University Medical Center offers compassionate treatment with infusions of unmanipulated cord blood cells to children diagnosed with a variety of neurodevelopmental disorders, including Hypoxic Ischemic Encephalopathy (HIE), Hydrocephalus, Apraxia, Cerebral Palsy (CP), and Autism Spectrum Disorder (ASD)6. Families of children with these conditions seek off-trial treatment under the FDA-approved Expanded Access protocol NCT03327467 that is based on nine previous clinical studies at Duke6.  Patients can only participate if they have privately stored their own cord blood or cord blood from a full sibling, and provided that the cord blood unit meets the eligibility criteria.

Families of children with neurodevelopmental disorders form a large community, due to the prevalence of the covered conditions. According to the CDC, among 8-years-olds in the United States, 1 in 345 have cerebral palsy, and 1 in 54 are on the autism spectrum7,8.  It is estimated that the number of people living with these conditions in the United States is 0.8 million for cerebral palsy and 3.5 million people on the spectrum. Because these are life-long conditions, children with significant developmental disabilities could potentially benefit from cell therapy at any point during the years when their brains are building neural connections, which is a drastic contrast to cancer therapies that are only delivered to patients in their moment of dire need.

Consumer demand for compassionate cord blood cell therapy of neurodevelopmental disorders far exceeds the capacity of the hospital-based expanded access program at Duke. Over the 3.5 years since the Oct. 2017 approval of the EA protocol, only 464 children have been treated, whereas over 17,000 families have joined a waiting list6. In early 2021, Duke signed a technology transfer licensing agreement with the biotech company Cryo-Cell International9. Under the terms of the agreement, Cryo-Cell would open at least one infusion clinic capable of providing expanded access treatments to over 1500 children per year, and Cryo-Cell would invest in further clinical trials that pursue full FDA approval of the therapy.

While the licensing agreement between Duke and Cryo-Cell is a big win for increasing patient access, it has also triggered big controversies. The biggest source of controversy is the fact that families are being charged a fee of $15,000 for the treatment6. Duke had been charging families this price for several years, and while it was well-known in the patient community, it managed to fly under the public radar. Once Cryo-Cell announced that they would charge the same price at their infusion clinic, the fee caught the attention of numerous biotech reporters and became well-known. Now there are ethical objections from many stakeholders that the access fee takes advantage of vulnerable families. There is one scientist in the cell therapy community who has blogged repeatedly that the evidence for the therapy is weak and therefore it should not have an expanded access approval6. On top of everything else, there are patient advocates who are offended by therapies that might “cure” autism, because among high-functioning people on the autism spectrum it is simply a neurodiversity and not a disability6.  These many voices have created a swirl of controversy around a program which is, at this time, probably the largest recruiting Expanded Access program in the advanced cell therapy field.

In many ways, the Duke/Cryo-Cell Expanded Access program for neurodevelopmental disorders is a microcosm of the challenges that arise when an Expanded Access program creates so much patient demand that it is difficult for the therapy developer to cover the costs of providing compassionate treatments. These are exactly the sort of issues that Ax-S Pharma was created to tackle. Ax-S Pharma is the leading education resource in the topic of pre-market expanded access to regulated medicines. The company produces workshops, conferences, and live online events. Its membership-based online hub provides video tutorials and case reviews as well as written references on the topic. Ax-S Pharma serves biopharmaceutical and healthcare professionals, policy makers, advocates, and members of the public.


  1. Verter F. Expanded Access Programs for Advanced Cell Blog Published 2021-11-06
  2. Jacobson CA, Hunter BD, Redd R, et al. Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. J Clin Oncol 2020; 38(27):3095-3106.
  3. Charrot S, Hallam S. CAR-T Cells: Future Perspectives. Hemasphere 2019; 3(2):e188
  4. Nietfeld JJ, Pasquini MC, Logan BR, Verter F, Horowitz MM. Lifetime Probabilities of Hematopoietic Stem Cell Transplantation in the U.S. BBMT 2008; 14(3):316-322.
  5. Harrison RP, Zylberberg E, Ellison S, Levine BL. Chimeric antigen receptor–T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods. Cytotherapy 2019; 21(2):224-233.
  6. Verter F. Parent’s Guide to Duke’s Research and Expanded Access Program of Cord Blood Therapies for Neurodevelopmental Disorders. Parent’s Guide to Cord Blood Foundation Newsletter Published 2021-11-15
  7. Data and Statistics for Cerebral Palsy. Web page Last updated 2020-12-31
  8. Data & Statistics on Autism Spectrum Disorder. Web page Last updated 2020-09-25
  9. Cryo-Cell. Cord Blood Banking Leader Cryo-Cell International Enters Into An Exclusive License Agreement with Duke University. GlobeNewsWire Released 2021-02-26
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