Where Commercial Stem Cell Clinical Trials Have Been, and Where They're Going: A Quantitative AnalysisSeptember 12, 2013
Updates: 9/16/2013: In response to reader feedback the section discussing specific cell types was temporarily deleted while we evaluated an alternative classification scheme for cell types employed in stem cell clinical trials. 9/20/2013: A revised discussion of specific cell types was added, including Fig. 10 and Table I.
Part II: Cell Types and Indications (Cardiovascular)
Classifying the 196 clinical trials in our database into major medical classes according to an ontology patterned on the U.S. National Library of Medicine's Medical Subject Headings controlled vocabulary (MeSH) reveals cardiovascular indications to predominate among all-time stem cell trials in our database (33%), with central nervous system diseases (14%) presenting the main competition to cardiovascular indications. Immunotherapy, wounds and injuries, gastrointestinal diseases, and musculoskeletal diseases combine to account for nearly another third of all trials (32%; Figure 5).
Figure 5: Distribution of trials by major medical indication classes, broken down by cell type. Blue: allogeneic cells; red: autologous cells. Total exceeds 100% because these classes are not mutually exclusive (e.g., Type 1 diabetes is classified as both a metabolic disease and an autoimmune disease). Three trials, employing stem cell-modulating drugs rather than cells, are not included in the data of this figure.
Autologous cell types dominate cardiovascular trials (68% of those trials) and are significant players in trials involving wounds and injuries (50%), gastrointestinal diseases (44%), and immune system and musculoskeletal diseases (30% and 27% percent of trials involving those diseases, respectively).
With respect to specific cardiovascular indications, peripheral vascular disease and myocardial infarction are the major targets addressed by trials in our database (22 and 18 trials respectively, 34% and 28% of all cardiovascular trials, or 11% and 9% of all trials), and autologous cells account for 50% or more of trials for each specific cardiovascular indication (Figure 6).
Figure 6: Distribution of cardiovascular trials by specific indication, broken down by cell type. Blue: allogeneic cells; red: autologous cells.
As Figure 7 illustrates, trials of autologous cells for cardiovascular indications grew explosively from 2005 to 2007 (during which period they went from 0% to 37% of all stem cell trials to date), but since then have been consistently in decline. In contrast, trials of allogeneic cells for cardiovascular indications, which commenced at nearly the same time, have shown slower but much more consistent growth as a fraction of all trials. It is tempting to suppose (but remains to be documented) that the widely assumed safety of autologous cells, combined with the comparative simplicity of autologous cell trials (particularly for minimally manipulated cells, which constitute a substantial fraction of these trials), may have encouraged a large number of modestly funded players to launch autologous cardio trials early on, poor outcomes or lack of funding tending to discourage subsequent efforts. Conversely, it may be that allogeneic cells have been slower out of the gate due to the greater complexity of developing them for human trials.
Figure 7: Allogeneic (blue) and autologous (red) cell trials in cardiovascular disease as a cumulative fraction of all trials to date for all indications, by start date. Note that 2013 data do not cover a full year (extending only through August).
Cardiovascular trial starts have consistently averaged about 8 per year since 2006 (Figure 8). Peripheral arterial disease and myocardial infarction are leading indications among all-time cardiovascular trials by virtue of both an early start (2005-2006) and a relatively consistent rate of new starts subsequently. In contrast, dilated cardiomyopathy is a more recent candidate indication (first launched in 2011), while ischemic cardiomyopathy, coronary artery disease, and compartment syndrome have not attracted consistent interest through the years.
Figure 8: Cardiovascular trial starts, per year, broken down by specific indication. Note that 2013 data do not cover a full year (extending only through August).
The number of companies launching cardiovascular trials grew explosively in 2006 (from 1 to 6 companies), and has shown a more moderate growth trend since then, reaching an all-time high of 10 companies launching CV trials last year (Figure 9).
Figure 9: Companies launching new cardiovascular trials, by year. Note that 2013 data do not cover a full year (extending only through August).
Viewed at a high level, mesenchymal stem cells (MSCs) have long dominated stem cell cardiovascular trials, comprising 57% of all trials (Figure 10), with hematopoietic stem cells (HSCs) and bone marrow concentrate (BMC) tied for second place at 14% each. Three new classes of therapeutics have recently (2012-2013) added greater diversity to the cardiovascular landscape: Capricor's cardiosphere-derived stem cells (CDCs) for myocardial infarction, ReNeuron's neural stem cells for peripheral arterial disease, and Polyphor's small-molecule drug, a CXCR4 antagonist intended to mobilize the patient's own stem cells following a myocardial infarction.
Figure 10: Cardiovascular trial starts per year, broken down by major cell type. Note that 2013 data do not cover a full year (extending only through August). See Appendix A for a detailed description of our cell-type classification scheme. Abbreviations: BMC: bone marrow concentrate; CDC: cardiosphere-derived cell; HSC: hematopoietic stem cell; MNC: mononuclear cells; MSC: mesenchymal stem cell; NSC: neural stem cell; O-D: other (drug).
Table I presents a more detailed view of the specific cell types included under the major categories of Fig. 10. See Appendix A, Cell Type Nomenclature for a detailed explanation of our cell preparation naming conventions.
Table I: Cardiovascular trial starts per year, broken down by specific cell types. Note that 2013 data do not cover a full year (extending only through August). See Appendix A for a detailed description of our cell-type classification scheme and the abbreviations employed here. Click any column label (year) or row label (cell type) to view its cardiovascular trials.
|Hematopoietic Stem Cell (HSC) Preparations|
|Mesenchymal Stem Cell (MSC) Preparations|
|Mononuclear Cell (MNC) Preparations|
COMING SOON - Part III in this series: - Cell Types & Indications (CNS)Tweet