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 reports (due to accidental detection of trials which were not captured initially). Please refer to this report as the latest update.

Total number of trials
Total number of cell therapy trials, registered in international databases, continue to increase. From 2011 to 2013 a total number of trials increase about 2 times.

trends13_total#

The value of US NCT database (ClinicalTrials.gov) remains constant over the years, representing 74% of all registered cell therapy trials internationally.

Sponsorship
The number on industry-sponsored clinical trials significantly increased in 2013, compared to previous two years. In the same time, the number of academic trials continue to grow even more rapidly.

total#_2013

Demographics
As in the previous 2 years, US and China dominated all other countries in number of cell therapy trials in 2013. However, the US trend is positive, but China’s trend is negative. Interestingly, Japan made a biggest jump up in 2013. South Korea, UK and Iran stay pretty much flat over last 3 years.

This graph shows a value of the most representative countries in % of total trials number.
trends13_countries

If we look at regions in general, we will not able to see significant fluctuations in the last few years. I’d only notice a shrinkage of Europe in 2013.

trends13_regions

Cell types
In order to demonstrate some interesting trends I’ve picked the most frequently used cell types in clinical trials. Mesenchymal stromal cells (MSC) trials continue to surpass all other cell types. In 2013, T-cell trials continued to grow slowly and represented the second most frequent cell type after MSC. The mostly rapidly growing cell types were bone marrow mononuclear cells (BM MNC) and dendritic cells (DC). DC were the “biggest movers” in 2013. Interest to hematopoietic stem/ progenitor cells (including mobilized blood, cord blood and bone marrow) dropped significantly in 2013. NK cells and adipose stromal vascular fraction (SVF) went up in 2013. Embryonic stem cell trials plunged to zero.

trends13_cells

Indications
Malignancies is the most frequent indication for cell therapy trials. It skyrocketed in the last 3 years (increase about twice every year)! 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 neurology, cardiovascular medicine and ophthalmology remains pretty much flat. Muskoloskeletal diseases have a prominent positive trend. Interest to cell therapy for liver diseases seem to be decreasing.

trends13_indications

It was a snapshot of dataset analysis for the last 3 years. I’ve picked only some trends to demonstrate that the data could be “sliced and diced” in many different ways.

How to cite:
Bersenev Alexey. Trends in cell therapy clinical trials 2011 – 2013. CellTrials blog. March 2, 2014. Available: http://celltrials.info/2014/03/02/trends-2011-2013/

{ 4 comments }

Role of monocytes in regenerative cell therapies

by Alexey Bersenev on February 16, 2014 · 0 comments

in cord blood

As I’ve written before, we largely don’t know what cell population underlies the mechanism of action of bone marrow or cord blood transplantation in regenerative medicine. Before infusion in neurological, cardiac, hepatic and other conditions, cord blood or bone marrow usually undergo minimal processing – red blood cells and platelet depletion. What remains before infusion is so-called mononuclear fraction (MNC) – a mix of white blood cells. It would be too naive to assume that only stem cells from MNC will do all “therapeutic job”. In reality, we have no idea what the value of different MNC populations in therapeutic effects. Recent study shed some light on this puzzle. The authors demonstrated that cord blood monocytes are essential in neuroprotective effect in stroke model.

Multiple independent groups have demonstrated before, that human cord blood MNC can ameliorate neurological deficit in stroke model. Now researchers used an elegant strategy to figure out the therapeutic value of different cord blood MNC populations. Using magnetic sorting (MACS) strategy, they depleted monocytes (CD14+), T-cells (CD2+), B-cells (CD19+) or stem cells (CD133+) from human cord blood MNC fraction. Whole unfractioned MNC and all different MNC fractions were infused in rat stroke model. Infarct size and behavioral tests were performed before and after cell therapy. Results were the following:

Activity levels and infarct size of the animals treated with monocyte depleted HUCB MNC were similar to that observed in the untreated MCAO group. When animals were treated with enriched fractions of CD14 + cells infarct size decreased to the same extent as with the MNC treated group. These results suggest that HUCB monocytes are the critical cellular component of HUCB MNC fraction that induces recovery after MCAO.

The authors observed the same results when they used CD14+ monocytes, derived from peripheral blood. It means that therapeutic value of monocytes did not depend on cell source. Unfortunately, study does not provide conclusive data (because of MACS inefficiency) about value of T-cells and stem cells:

Our data in those animals that received the CD133 (stem cell) and CD2 (T cell) depleted HUCB preparations do not allow us to draw any firm conclusions about the role of these cells in HUCB induced recovery after MCAO since the MACS sorting only depleted 52.9% and 22.3% respectively of these cells from the MNC fraction.

This is not the first study, which highlights therapeutic value of monocytes. Two studies (Award 2006 and Sanchez-Guijo 2010) demonstrated that human blood CD14+ and mouse bone marrow CD11b+ cells improve angiogenesis in hind limb ischemia models, irrespective of administration route (i.v. or i.m.). In the cardiac clinical trial, improvement of heart function was linked to monocyte content in bone marrow-derived MNC, but not to lymphocytes or stem cells number. In all these cases, there were no evidence for cell integration, engraftment and persistence.

The results of this and other similar studies support my view on defining “stem cell therapy” in relation to mechanism of action. When we use MNC fraction (from peripheral blood, cord blood, bone marrow, adipose SVF) in regenerative medicine, we have now more evidence for therapeutic value of mature cells (such as monocytes) than for the stem cells.

{ 0 comments }

Cell therapy clinical trials – 2013 Report

by Alexey Bersenev on February 1, 2014 · 9 comments

in annual reports

This is 2013 report of registered clinical trials in cell therapy. Every year I overview some tracked data from international clinical trials databases. You can see previous annual reports here.

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, 2013 to Dec. 31, 2013 in international databases.

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

  • hematopoietic cells for recovery of blood formation in hematological malignancies;
  • gene-modified hematopoietic cells for correction of metabolism errors and inherited immune disiseases (example: SCID);
  • ex vivo expanded hematopoietic cells for enhancement of engraftment in hematological malignancies;

2. Platelet rich plasma trials
3. Extracorporeal devices with cells

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”

Total number of trials tracked: 323
Number of duplications between databases: 7

Databases
The following databases were scanned:
US NCT (NIH-FDA)
European EUCTR (EudraCT)
Japanese UMIN, JMA CCT, Japic
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:

databases13

Demographics:

countries13

regions13

Sponsorship
All trials were divided on 2 categories – “academic” and “industry”. The term “academic” combined any monetary support (governments, funds…) other than “company-sponsored” (“industry”). Term “industry” also included companies – collaborators, when sponsorship is not clear from trial description and when company manufactured/ provided cellular material.

sponsor13

Cell types
More than 30 different cell types were assessed in clinical trials in 2013. Some trials included more than one cell type (in different groups or mixed).

majorcelltypes13

MSC13

immunecells13

othercelltypes13

donortype13

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; iPS – induced pluripotent stem cells; MAPC – multipotent adult progenitor cells.

Indications:

indications13

Special considerations:

  1. This is a snapshot of some data, which I’ve been collecting during the year. If you would like to collaborate on data mining, please contact me.
  2. These data were not validated by independent expert.
  3. How to cite: Bersenev Alexey. Cell therapy clinical trials – 2013 report. CellTrials blog. February 1, 2014. Available: http://celltrials.info/2014/02/01/2013-report/
  4. You’re free to share these data with appropriate credit under CC BY-ND 3.0 license.

You can follow real time updates via @CellTrials

{ 9 comments }

Cell therapy trials failures in 2013

December 25, 2013

At the end of the year, I want to bring your attention to major failures and setbacks for cell therapy field in 2013. This is an attempt to capture the vast majority of failed clinical trials. This overview is based on (i) results reported in literature (via PubMed) or (ii) companies press releases and (iii) […]

Read the full article →

Trends in cord blood enhancement 2013

November 10, 2013

I’m following with a big interest the latest development in technologies for cord blood (CB) enhancement in hematology. “Enhancement” means boosting a therapeutic value of cord blood graft via its stimulation/ modification (homing, migration, engraftment) or increase cell number (expansion, processing optimization). Today, I’m going to overview very recent trends and give update on methodologies […]

Read the full article →

Hurdles in conducting of cell therapy trials for acute neurological conditions

October 20, 2013

Acute neurological conditions, such as stroke and traumatic brain injury (TBI) is an attractive target for cell therapy. Success of pre-clinical models allowed to move to clinical trials relatively quickly. Industry also sees a great opportunity in this direction. For example, Athersys and Cytomedix have active ongoing Phase 2 trials. However, the trials did not […]

Read the full article →

Failure of autologous cord blood transplant in diabetes

October 13, 2013

I’ve written about trials, assessing autologous cord blood transplantation (CBT) in pediatric type 1 diabetes. The results of first such trial, conducted by University of Florida in collaboration with NIH, were disappointing. The results of another trial, conducted in Germany and utilized the same protocol, have been published very recently. And as US trial, this […]

Read the full article →

Grafix – a hype or revolution in medicine?

August 17, 2013

A new press release of US-based Osiris Therapeutics boost a value of the company more than twice overnight. The price per share skyrocketed from $10 to $25 (+140%) in a single day – August 13. This is a very rare case for cell therapy industry and it made me wonder – why did it happen? […]

Read the full article →

Stem cell therapy in multiple sclerosis – no immune re-installation

August 4, 2013

Stem cell-based therapy of multiple sclerosis (MS) is a very hot topic. There are a lot of clinical trials going on right now all around the world. Considerably, MS is autoimmune disease, where auto-reactive T-cells enter central nervous system and attack myelin. This auto-aggression leads to inflammation and, eventually, to neurodegeneration. Pathogenesis-based concept behind of […]

Read the full article →

Flaws and errors in cardiac cell therapy reporting – Interview with Darrel Francis

July 22, 2013

Darrel Francis – Professor of Cardiology at the Imperial College London. He is a senior author of the recent report, which challenges the validity of research and clinical trials in cardiac cell therapy, conducted by Bodo-Eckehard Strauer’s group. He kindly agreed to answer my questions. 1. Dr. Francis, What is your interest in cardiac cell […]

Read the full article →