Analyzing the
Business and Technology
of Stem Cells

Fifteen Years, 60 Companies, 196 Trials (Part III)

Where Commercial Stem Cell Clinical Trials Have Been, and Where They're Going: A Quantitative Analysis

September 23, 2013  

Part III: Cell Types and Indications (Central Nervous System)

< Part II: Cell Types & Indications (Cardiovascular)                                 Part IV: Dataviewer >

As we have reported elsewhere in this series [Part II: Cell Types & Indications (Cardiovascular), Fig. 5], central nervous system (CNS) indications are the second most prominent area of commercial stem cell clinical trials, accounting for 14% of the 196 trials in our database (compared to cardiovascular's 33% share). Unlike cardiovascular trials, where autologous cells account for the large majority (68%) of trials, CNS trials predominantly employ allogeneic cells (64% of CNS trials; Figure 11) - due in part, no doubt, to the fact that neural stem cells have not yet proven practical to harvest non-destructively from patients (neural stem cell preparations are typically derived from post-mortem fetal or adult nervous tissue). This may change in future, however, as protocols for deriving neural cells from embryonic or induced pluripotent stem cell lines evolve.

Figure 11: Distribution of CNS trials by specific indication, broken down by cell source. Blue: allogeneic cells; red: autologous cells.

Three indications (stroke, spinal cord injury, and amyotrophic lateral sclerosis, or ALS) account for the lion's share (79%) of all CNS trials to date. They contribute in about equal measures to CNS trials to date, despite the fact that only one (stroke) represents a large market opportunity (Americans suffer about 610,000 first strokes annually, compared to just 12,000 spinal cord injuries and 5,000 new cases of ALS).

The dominance of allogeneic cells in CNS trials has been a constant since the field's earliest days (Figure 12).

Figure 12: Allogeneic (blue) and autologous (red) cell trials in central nervous system 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).

Unlike cardiovascular trials, which have seen a fairly constant rate of annual new trial starts over the years [Part II: Cell Types & Indications (Cardiovascular), Fig. 8], CNS trial starts peaked sharply in 2011, due entirely to a one-time burst in new stroke trials, and more recently have declined just as rapidly (Figure 13). Spinal cord injury and ALS trials have been the most consistent contributors to annual new CNS trial starts.

Figure 13: CNS trial starts, per year, broken down by specific indication. Note that 2013 data do not cover a full year (extending only through August).

The pattern of trial starts per year illustrated in Figure 13 is precisely paralleled by the numbers of companies launching CNS trials per year (Figure 14).

The most active companies in the CNS space (those with more than one trial) include:

Figure 14: Companies launching new CNS trials, by year. Note that 2013 data do not cover a full year (extending only through August).

Perhaps somewhat counterintuitively, neural stem cells (NSCs) have been a relatively minor player in CNS trials to date (29% of all CNS trials), far outnumbered by mesenchymal stem cells (MSCs; 54%), which witnessed a burst of new trial starts in 2011 and 2012 (Figure 15). It remains to be seen whether MSCs' prominence in CNS trials (roughly equal to that of MSCs in cardiovascular trials; see [Part II: Cell Types & Indications (Cardiovascular), Fig. 10]) is actually due to their suitability for this indication or whether, instead, it primarily reflects their fairly unencumbered intellectual property status (relative to NSCs).

Figure 15: CNS 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: ESC: embryonic stem cell; HSC: hematopoietic stem cell; MNC: mononuclear cells; MSC: mesenchymal stem cell; NSC: neural stem cell.

Geron's Phase 1 trial of embryonic stem cell-derived cells for spinal cord injury made history as the first stem cell trial employing ESCs. It proved ill-fated, however: in 2008 the FDA imposed a safety-related clinical hold on the trial prior to treatment of its first patient (the hold was subsequently lifted in 2010), and in 2011 the company announced it would abandon its stem cell therapeutics development program entirely. Geron's shuttered ESC program is now in the process of being acquired by BioTime, Inc.

< Part II: Cell Types & Indications (Cardiovascular)                                 Part IV: Dataviewer >