the company intends to begin an intermediate-stage trial in 2014, with full follow-up completed by mid-2016. If the data look good, Stem Cells would then work with the FDA to plan a final, pivotal trial.
Compared to Stem Cells’ other programs in clinical trials, a treatment for macular degeneration would be likely to open the largest market for the company, McGlynn says. The disease is the leading cause of vision loss for people over 55. As many as 90 percent of those with macular degeneration have the dry form, while about 10 percent suffer from the wet form of the disorder, which can be treated with drugs that slow the rate of vision loss in some patients. The numbers of patients needing treatment are expected to rise, because the disease risk increases as people get older.
“The population, of course, continues to age,” McGlynn says.
Macular degeneration is a complex disease whose roots have been traced to genetics, diet, and other factors such as smoking. Eye doctors can spot the early trouble signs of the disorder during a routine eye exam. As people age, small yellow deposits called drusen often appear beneath the retina. Medium-sized drusen suggest the onset of macular degeneration. However, vision may not be affected until these deposits become larger.
In the late stage of macular degeneration, the light-detecting photoreceptors in the macula may break down, and the damage can also be seen in the supporting cell layers of the macula, such as the retinal pigment epithelium cells.
In the wet form of the disease, abnormal, leaky blood vessels form underneath the retina. FDA-approved drugs for wet macular degeneration such as Genentech/Roche’s ranibizumab (Lucentis) and Regeneron’s aflibercept (Eylea) are injections designed to limit the growth of these blood vessels, which can lead to rapid and severe vision impairment.
Vision loss can also be substantial from the later stage of the dry form of macular degeneration, but no treatments have yet been approved. In the drive to find effective remedies, Stem Cells has competitors not only from drug companies but also from other stem cell programs.
Santa Monica, CA-based Advanced Cell Technology (OTCBB: [[ticker:ACTC]]) launched its own trial of a stem cell-derived treatment for dry macular degeneration in 2011, and received the go-ahead in July from a safety monitoring board to expand enrollment of the small study. In its cell injection, Advanced Cell Technology uses retinal pigment epithelial cells derived from human embryonic stem cells. This approach is more common than Stem Cells’ strategy.
Stem Cells extracts human neural stem cells from donated fetal brain tissue. In nature, these pluripotent stem cells have the potential to differentiate into a range of central nervous system cells, so they have been seen as a source of possible replacement cells in people impaired by disease or injuries.
In animal studies that laid the groundwork for its clinical trial in macular degeneration, Stem Cells found that its neural stem cells, after injection into the eye, spread out “like a necklace” between the macula and the layer of retinal pigment epithelium cells, McGlynn says. The neural stem cell layer appeared to protect the photoreceptor cells from deterioration and stave off vision loss in rats that are bred to develop a condition similar to macular degeneration in humans, according to a 2012 research paper on the study. The researchers found no evidence of uncontrolled growth among the injected cells. Unbound cell growth, and even tumor formation, are potential risks of stem cell treatments.
In Stem Cells’ clinical trial, vitreal surgeons use a “tiny needle” to inject the suspension of stem cells, in a procedure that takes about an hour, McGlynn says. Participants take a short course of immune suppression drugs to guard against immune system rejection, because the stem cells come from donor tissue rather than from the host’s own cells. But Stem Cells has found no signs of immune system reactions after the immunosuppressant drugs are discontinued, McGlynn says.
In the meantime, drug developers have been testing experimental remedies based on advancing insights into the causes of dry macular degeneration. For example, New York drug giant Pfizer is testing an antibody against a compound called amyloid beta, which is well-known as a factor in Alzheimer’s disease, but is also an ingredient found in drusen.
In another project, Seattle, WA-based Acucela is conducting mid-stage clinical trials of an oral drug, emixustat or ACU-4429. The drug is designed to slow down certain processes in the photoreceptor cells that can lead to a buildup of toxic byproducts including A2E, which has been linked to macular degeneration.
McGlynn says he’s not concerned that a successful new drug could pre-empt the market in dry macular degeneration. There may be room for a number of different therapies, including small molecules, cell-based remedies, and biologic drugs, he says.
“It’s all good,” McGlynn says. “There are very few agents I’m aware of that are the silver bullet for any disease or condition in humans.”
