Post updated on Feb. 17, 2015

Today I’m sharing some of my data for the last 4 years. This is a snapshot of trends in cell therapy trials from 2011 to 2014. This year, I’m planning to make few posts on cell therapy trends. I’d like to analyze some trends in mesenchymal stromal cells, adipose tissue-derived cells, industry versus academia and, finally, get to results of the trials. Some of these posts we will find on StemCellAssays.

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Total number of trials
Total number of cell therapy trials, registered in international databases, continue to grow from year to year. From 2011 to 2014 a total number of trials increase more than 2 times. In 2014, every day cell therapy trial got registered in database. Please note that “registered” is not necessarily “new”.

trends14_total#

About 75% of all databases cell therapy listings posted on US-based NCT registry (ClinicalTrials.gov). The contribution of NCT database remains constant over the years, with range of 71-79% from all cell therapy trials, registered worldwide.

Demographics
Similarly to the previous 2 years, US and China dominated all other countries in number of cell therapy trials in 2013. The US trend is keep going up, but China’s trend is getting flattened. Japan, South Korea and UK went down in 2014.

This graph shows a value of the most representative countries as % of total trials number.

trends14_countries

There is no big difference from year to year in contribution by regions of listed cell therapy trials. However, the value of North America (read USA) steady increased from 28% to 36%.

trends14_regions

Cell types
The positive trend for 2 “major advancers” – mesenchymal stromal cells (MSC) and T-cells is continued. T-cell curve looks especially impressive. MSC trials continue to surpass all other cell types in 2014. Another steady growing cell type is adipose-derived cells – very good positive trend. It seem like field lost interest to bone marrow mononuclear cells (BM MNC) and dendritic cells (DC) in 2014. Yet another decliner is NK cells. Embryonic stem cell trials are coming back! Three ESC trials were registered in 2014.

trends14_cells

Indications
Malignancies is the most frequent indication for cell therapy trials. It skyrocketed in the last 3 years (increase about twice every year) with some decline in 2014. Of course, it coupled with interest to cellular immunotherapy and strictly correlates with use of immune cells (T-cells, DC, NK cells…). Interest to cell therapy in cardiovascular medicine remains pretty much flat. Muskoloskeletal diseases have a prominent positive trend. Yet another “advancer” of 2014 is neurology. Interest to cell therapy for liver diseases seem to be decreasing.

trends14_indications

It was a snapshot of dataset analysis for the last 4 years. I’ve picked only few trends to demonstrate that the data could be “sliced and diced” in many different ways. Stay tuned for some other interesting results and trends!

How to cite:
Bersenev Alexey. Trends in cell therapy clinical trials 2011 – 2014. CellTrials blog. February 14, 2015. Available: http://celltrials.info/2015/02/14/trends-2014/

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Cell therapy clinical trials – 2014 Report

by Alexey Bersenev on January 22, 2015 · 4 comments

in annual reports

This is 2014 report of registered cell therapy clinical trials. Every year I give a snapshot of some tracked data, captured from international clinical trials databases. You can see previous annual reports here.

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Definitions and criteria
I tracked clinical trials which fall in definition of cell therapy: administration of living cells in human with therapeutic purpose. Besides “traditional cellular products”, I also included tissue engineered constructs with cells, cellular gene therapy and use of cells as a vehicles for therapeutic agent delivery. I tracked all clinical trials which were registered from Jan.1, 2014 to Dec. 31, 2014 in international registries.

The following categories were excluded from analysis:
1. Cells for homologous use:

  • hematopoietic cells for recovery of blood formation in hematological malignancies or for recovery of hematopoiesis after chemotherapy for treatment of solid tumors;
  • gene-modified hematopoietic cells for correction of metabolism errors and inherited immune diseases (example: SCID);
  • ex vivo expanded hematopoietic cells for enhancement of engraftment in hematological malignancies;

2. Platelet rich plasma trials
3. Extracorporeal devices with cells (no administration of cell inside of body).

Data mining strategy
“Hand coding” included:

  • using multiple key words and phrases
  • exclusion of overlaps between search results
  • exclusion of duplications between databases
  • reading trial description and “coding” the following categories: trial ID, country, phase, status, indication, cell type, donor type, type of sponsorship, name of company-sponsor, study acronym, number of patients in enrollment.

Key words:

    • “cell therapy”
    • “stem cell”
    • “cord blood”
    • “umbilical cord”
    • “bone marrow”
    • “cancer vaccine”
    • “tissue engineering”
    • “cellular”
    • “mesenchymal”
    • “adipose”

by name of company

Total number of trials tracked: 372
Number of duplications between databases: 8

Databases
The following databases were scanned:
US NCT (NIH-FDA)
European EUCTR (EudraCT)
Japanese UMIN, JMA CCT
Indian CTRI
Chinese ChiTCR
Iranian IRCT
Australian/NZ ANZCTR
UK ISRCTN
Dutch NTR
South Korean CRIS

All international databases, except NCT, were scanned via WHO Search Portal (ICTRP). Each database was checked separately to capture everything, missed by ICTRP.

Databases representation:

databases14

Demographics:

countries14

regions14

Sponsorship
All trials were divided on 2 categories – “academic” or “industry”. The term “academic” combined any monetary support (governments, funds, charities…) other than company-sponsored. Term “industry” also includes (1) companies – collaborators, when sponsorship is not clear from trial description and when company manufactured/ provided cellular material, (2) commercial for-profit clinics with unclear regulatory authorization.

sponsorship14

Cell types

donortype14

majorcelltypes14

MSC14

immunecells14

othercells14

Abbreviations: MSC – mesenchymal stromal cells, HSPC – hematopoietic stem/ progenitor cells, TIL – tumor-infiltrating lymphocytes, DC – dendritic cells, BM – bone marrow, MNC – mononuclear cells, NK – natural killer cells, CIK – cytokine-induced killers, SVF – stromal vascular fraction; MB – mobilized blood; T-regs – regulatory T-cells; ESC – embryonic stem cells; CAR – chimeric antigen receptor; CB – cord blood; DLI – donor lymphocyte infusion.

Indications:

indications14

This is a first snapshot from 2014 report. I’m planning to post trends analysis, trials results analysis and some other data. Stay tuned!

How to cite:
Bersenev Alexey. Cell therapy clinical trials – 2014 report. CellTrials blog. January 22, 2015. Available: http://celltrials.info/2015/01/22/2014-report/

You’re free to share these data with appropriate credit under CC BY-ND 3.0 license.

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One clinical study, which was released 2 weeks before Christmas holidays captured my attention (but not attention of mass media). One of the most scandalous Indian “stem cell tourism” clinic Nutech Mediworld published(!) results of the study, which evaluates embryonic stem cell transplantation in children with cerebral palsy. Yes, you’re reading it correctly – embryonic stem cells in children! Now, I have no idea how this study was approved by Independent Ethics Committee (as stated in the paper) and how this manuscript passed peer review of Journal of Translational Medicine, but here is the fact – study is done and results are published. I think, we should at least read it, try to analyze it (it’s not easy!) and maybe discuss it. Before we dive into the study, I’d like to give you a little bit of background.

Geeta Shroff – a director of Nutech Mediworld – is a highly controversial and highly criticized by “westerners” figure in “stem cell tourism”. She is “a retired obstetrician and self-taught embryonic stem cell practitioner”, who used to be skeptical about sharing data with peers:

Dr. Shroff does not share data, has not submitted to peer review (she’s said she has “no peers”) and has performed no controlled clinical trials. While patients call her a saviour, other researchers call her a quack, a fraud or names even less flattering.

Well, seem like she changed her mind lately. I remember, that many “critics” refused to believe that actual embryonic stem cells (ESC) were used by Nutech. They thought that Nutech used term “embryonic” for fetal cells, derived from aborted material. But, according the paper it’s real single ESC line, derived from preimplantation embryo post IVF.

Let’s move to the study. As I mentioned above, study protocol was approved by Ethics Committee. Also, it was reported to “National Apex Body” (I don’t know what is it, but sounds like something on government level). Yet another interesting fact – the last author of the paper is a government worker (Ministry of Home Affairs, Government of India). I’d like to remind you that this is not the first “embryonic stem cell study” from India. So, I think, one thing we have to realize is that if these kind of studies could be “shocking” and “hard to imagine” in US or Europe, it could be “normal” and totally acceptable for India or some other countries. Also, we have to realize that reporting of some particular number of patients (“cherry picking”?), treated in one particular “stem cell clinic” is very different from well designed clinical study or trial. We have no way to check how information, presented in the paper is accurate, since it’s not a registered trial and there is no (as far as I understand) oversight from any agency.

Next, I’d like to touch ESC product composition, which was used in kids with cerebral palsy. The authors did not bother much with differentiation of ESC into mature cells. In fact, transplanted ESC were Oct4+, SSEA3+, Nanog+, Sox+, betaHCG+, CD34+, Nestin+, GAF+ and NeuN+. So, it was a great mix of undifferentiated ESC and neurally induced progenitors. There is a reference to Shroff’s patent in the paper. If we look at this patent (which btw covers everything – all types of ESC derivatives and all kind of diseases), we can see that ESC product contains at least 40% of undifferentiated cells:

…in one embodiment, the portion of undifferentiated stem cells will be no more than about 80% of the total population of cells. In another embodiment, the portion of undifferentiated stem cells will be no more than about 40% of the total population of cells.

ESC progeny in the product are not characterized and could be hematopoietic, neural, mesenchymal, hepatic… Cells were infused and injected multiple times via all possible routes: intramuscular, intravenously, “intra-caudal”, as eye drops, as nasal spray, retro-bulbar, as oral or ear drops. Since, there was no immunosuppression, researchers check hypersensitivity to ESC product via skin probe before starting a treatment. One more interesting thing – the cells were cryo-stored in pre-filled syringes at -20C. There is no viability data in the paper.

91 children were included in the “study” with age from 1 month to 18 years with different degree and course of disease. The authors noticed functional improvement in all ages and starting scores of disease, based on functional scales (GMFCS-E & R). Also, they indicate improvement in cognition. Of course, we cannot make solid conclusions about efficacy, since it was not randomized and controlled trial. About 10% of patients had adverse events, such as swelling, itching, fever, chest congestion and others. However, there is no information about long-term safety and, especially, about such important potential complication as ESC-related excessive tissue growth. According the paper, about half of patients were not followed more than 3-6 months after the first treatment (did not return for 2nd and 3rd phases of treatment).

Of course, this “study” causes a lot of questions on every level – from ethical approval (without any pre-clinical animal studies) and study design to cell product characterization and clinical outcome. What puzzles me is that, apparently, Indian government agencies, as well as independent ethics committee were aware of the study and did not see any problem with it. I’d assume that Nutech itself did not see any problem with experimentation on children (for money!), because they had previous experience with ESC-based treatments of adults. Unfortunately, we cannot learn a lot from this study simply because of its design and lack of valuable information in the paper. I think, we as community should be aware of such “studies”, because it is a part of “cell therapy” or “stem cell therapy” or even “stem cell therapy industry”. What do you think of all this, guys?

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Cell therapy clinical trials failures in 2014

January 4, 2015

Today, I’d like to highlight the most interesting, in my opinion, clinical trials failures, reported in 2014. As field is moving to efficacy (Phase 2) trials, we are starting to see more failures. In this overview, I’m going to focus on efficacy results. I hope we can learn a lot from these failures and avoid […]

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Top 10 cell therapy clinical studies in 2014

January 2, 2015

At the end of the year I analyze results of clinical studies in cell therapy. Today, I’d like to highlight 10 most significant, in my opinion, clinical studies with published results. Taking in account excellent safety profile of most cellular therapies, I was trying to focus on efficacy and long-term outcomes. Do cells really work? […]

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Cell therapy highlights from #ASH14

December 8, 2014

Annual 56th meeting of American Society for Hematology (ASH) is about to finish in San Francisco. I was following conference via twitter and I was amazed by stream of tweets – very good tweets, high value tweets, unpublished data tweets, 1 tweet per second! There was no “scientific tweets”, but almost all were “clinical”. Here, […]

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Some thoughts on results of NeoStem cardiac cell therapy trial

November 19, 2014

In the last two days I was involved in lively twitter discussions about the results of Phase 2 PreSERVE-AMI clinical trial, sponsored by NeoStem. Unfortunately, interpretation of results divided professionals for two camps – (1) trial is failed and (2) trial is successful. Why did it happen? Maybe the truth somewhere in the middle? I’d […]

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Stem Cell Autopsy: Survival and fate of fetal neural stem cells in NeuralStem ALS trial

November 16, 2014

I’ve written two years ago about autopsy findings from ALS patients, treated by neural stem cell product candidate, commercialized by NeuralStem. Recently, company published an update on pathology of spinal cords and donor cell fate after transplantation. The article is freely available online. The authors analyze 6 postmortem cases of transplantation investigational product NSI-566 into […]

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Tracking results of clinical studies in cell therapy

May 11, 2014

It has been awhile since I called to collaborate and proposed to track results of clinical trials and studies. Unfortunately, nobody expressed an interest. So, starting from this year, I’ve attempted to do it myself. Today, I’m sharing results of the first 3 months of this experiment. Methodology: I track results of: published clinical trials; […]

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Trends in cell therapy clinical trials 2011 – 2013

March 2, 2014

Since last year, I’m sharing some trends in cell therapy clinical trials. Real time tracking of all registered trials allows to identify trends in multiple dimensions. Today I”m posting a snapshot of trending for the last 3 years – from 2011 to 2013. There could be some minimal discrepancies in numbers between this and previous […]

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