- Four biotech companies are pursuing the treatment of spinal cord injury with the use of stem cell transplantation.
- Each company demonstrated efficacy in pre-clinical studies.
- The race is in the early stages but InVivo Therapeutics is clearly leading the pack based on its strategic approach to accelerated HDE approval and initial trial results.
There are four small biotech companies vying to develop a new standard of care for spinal cord injury; InVivo Therapeutics (NASDAQ:NVIV), StemCells, Inc. (STEM), Neuralstem, Inc (CUR) and Asterias Biotherapeutics (AST). All four companies use some form of stem cell therapy as part of its overall therapeutic platform. What follows is a comparative analysis of each company.
Spinal Cord Injury Basics
First some spinal cord injury basics to set the foundation. As defined on the Mayo Clinic's website, "A spinal cord injury is damage to any part of the spinal cord or nerves at the end of the spinal canal -- often causing permanent changes in strength, sensation and other body functions below the site of the injury."
Spinal Cord Injury [SCI] comes in two types; complete injury, which means there is no function below the level of injury, and incomplete injury, which means there is some function below the level of injury.
In order to get a better perspective of various injury types and where they occur, below is a graphical picture of the spine and the areas of the body that are influenced:
The standard for determining the extent and severity of a patient's spinal cord injury is the ASIA Impairment Scale (see below).
A muscle grade of 3, which is the key distinction between ASIA C and ASIA D, is active movement through full range of motion against gravity.
In an extensive study of thoracic and lumbar injuries, only 22.4% of thoracic (T4-T9) or thoracolumbar (T10-T12) spinal cord injury patients improved one or more ASIA levels. Only 4.1% of ASIA A thoracic/thoracolumbar patients showed neurologic improvements. As you would expect, thoracic patients had the least potential for neurologic improvement.
Another large study of thoracic vs. cervical spinal cord injuries showed marked recovery (improvement of at least two grades from AIS at baseline at week 26) for ASIA A patients of 15.5% for cervical vs. 7.0% for thoracic. The study included both complete and incomplete injuries.
In addition to severity and location, time is a critical factor in neurologic improvement after injury. Shortly after injury and extending up to six months, there can be varying degrees of spontaneous recovery. When evaluating and comparing trial results among the different therapeutic approaches, it's important to keep in mind the possibility of spontaneous recovery.
StemCells and Neuralstem are pure play neural stem cell companies. They use adult neural stem cells in their therapeutic approach. The cells are transplanted directly into the spinal cord of spinal cord injury patients.
Asterias on the other hand uses oligodendrocyte progenitor cells. Oligodendrocyte progenitor cells are the precursors to oligodendrocytes, which support axons and provides a myelin sheath for nerve cells to improve transmission. Similar to StemCells and Neuralstem, the cells are transplanted directly into the spinal cord of spinal cord injury patients.
InVivo has taken a different approach compared to the other three companies. It uses a neuro-spinal scaffold, which is a bioresorbable polymer scaffold that is designed for implantation at the site of injury. The next phase of InVivo's approach will be to load neural stem cells onto the scaffold, thereby taking advantage of the beneficial properties of both therapies.
This is where the comparisons get interesting. It's hard to make an apples to apples comparison between companies with such diverse therapeutic approaches but results are results and they start with pre-clinical studies.
All four companies used the BBB locomotor rating scale, which provides a baseline for data comparison. Below are the results:
Each of the companies show improvement with their respective treatments. However, what jumps out to the reader is the degree of separation between InVivo's scaffold + high-dose hNSCs results and the control arm.
Rat models do not always correlate with human results and clearly there were different methodologies in the pre-clinical studies that may have skewed the data, but InVivo's results seem compelling above and beyond the other companies.
StemCells' trial criteria for Phase I/II were as follows:
- Thoracic spinal cord injury (T2-T11)
- AIS Grade A, B, or C
- Minimum of six weeks post injury.
- Must be stable stage of medical recovery after injury.
Neuralstem's trial criteria for Phase 1 are as follows:
- AIS A complete (T2-T12)
- At least 1 year but no more than 2 years from time of injury.
Asterias trial criteria for Phase I were as follows:
- AIS A complete spinal cord injury (T3-T11).
- Transplant 7-14 days post injury.
InVivo's trial criteria for its Pilot Study:
- AIS A complete spinal cord injury (T3-T12/L1) confirmed occurring within the past 21 days.
- Non-penetrating contusion injury no less than 4 mm diameter and limited to 2 continuous vertebral levels.
As indicated above, the main trial criteria have significant variability between each of the trials, which is important to consider when reviewing results.
StemCells announced positive results of its Phase I/II study on May 14, 2015. The company reported on seven AIS A patients and five AIS B patients. Three of the seven AIS A patients and four of the five AIS B patients showed signs of positive sensory gains. Two of the AIS A patients progressed to AIS B. Given that the patients must be in the stable stage of recovery, it is highly likely the improvements were the result of the treatment.
StemCells has initiated its Phase II proof-of-concept study, which will include cervical spinal cord injury patients grade A, B, or C with minimum 12 weeks post injury.
Trial was approved in November, 2014. No trial results to date.
The Phase I trial of five patients was completed with no serious adverse events. No major sensory neurological changes were observed.
The company initiated a Phase I/IIa study for patients with sub-acute complete cervical spinal cord injury. It will be dose escalating administered once between 14 and 30 days.
On July 6, 2015, InVivo announced significant improvement in the second and third patient. It had already been reported that the first patient had improved from AIS A to AIS C, which occurs in fewer than 5% of AIS patients with T10 - T12 injury. Based on the update, patient number three improved from AIS A to AIS B, which occurs in fewer than 4% of patients with a T4 injury.
It should be noted that InVivo's results, which appear exceptional are based on scaffold only. As previously mentioned, the company plans to load the scaffold with neural stem cells in future trials. Based on pre-clinical results, the addition of stem cells should substantially improve efficacy results.
InVivo's strategy around using the biomaterial scaffold before stem cells is also providing an accelerated path to commercialization. The company received humanitarian use device designation in 2013, which is a simpler and quicker path to approval by providing safety and probable benefit through the humanitarian device exemption (HDE). The timeline based on HDE approval is provided below,
I am long InVivo but had no preconceived notion of where this comparative analysis would take me. InVivo's scientific platform of using both a biomaterial scaffold and neural stem cells appears best in class when compared to the stem cell only approach. InVivo is not, however, a stem cell company presently. The corporate presentation states "InVivo plans to partner with a stem cell company to accelerate project timelines." Ultimately, InVivo will need a stem cell company to achieve maximum success. However, based on InVivo's early success with the scaffold only, the stem cell companies may need InVivo even more!
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