Stem Cells, Inc. Expanding Trial in Age-Related Eye Affliction
In the seven years since companies including Genentech/Roche and Regeneron launched new drugs to slow vision loss from an eye disorder called “wet” age-related macular degeneration, the market for those drugs has risen to an estimated $4 billion.
But that substantial market may some day be dwarfed by the revenues flowing to companies with new treatments that can thwart the earlier and much more common form of macular degeneration, dubbed the “dry” form, which also erodes vision as it progressively damages a key eye structure called the macula.
Not surprisingly, a pack of pharmaceutical giants and smaller biomedical companies are pursuing possible treatments for dry age-related macular degeneration (AMD), which afflicts an estimated 20 million to 30 million people worldwide. Competitors are testing different drug types, including antibodies and small molecules, and are targeting various biological mechanisms suspected as factors in the eye disorder.
Taking another tack, companies such as Newark, CA-based Stem Cells, Inc. (NASDAQ: STEM) are injecting preparations of live cells into the eyes of clinical trial participants with the dry version of the disorder. The hope is that these stem cells will incorporate themselves into the eye structure, and take on the work of a class of eye cells that normally maintain the health of the macula, a small but crucial spot near the center of the retina that is key to sharp central vision.
In the normal eye, maintenance cells called retinal pigment epithelium (RPE) cells help clear away waste products that can damage photoreceptor cells in the macula, says Stem Cells CEO Martin McGlynn. But if the maintenance cells malfunction, the waste buildup can cause the macula to atrophy, resulting in blind spots or blurred vision.
“The RPE layer is the main suspect in age-related macular degeneration,” McGlynn says.
Last year, the first participants in Stem Cells’ early stage trial of its experimental therapy received injections of 200,000 purified human neural stem cells beneath the retina in the back of the eye. The first goal of the trial, which began at the Retina Foundation of the Southwest in Dallas, TX, is to evaluate the safety of the company’s cell preparation, called HuCNS-SC.
Based on follow-up data from the first four trial participants, an independent safety committee late this year cleared the way for Stem Cells to begin injecting new participants with a higher dose of one million cells—the dose the company expects to use if the therapy proves successful in forestalling vision loss. Stem Cells has added the Byers Eye Institute at Stanford in Palo Alto, CA as a trial site, and has gained FDA permission to enroll participants at as many as three other US sites.
Stem Cells has also been testing its neural stem cells as treatments for other diseases. Its clinical trial in spinal cord injury, for example, started earlier than the trial in macular degeneration. But the eye studies will yield results more quickly than the programs in other diseases, McGlynn says, so the stem cell treatment for dry AMD may turn out to be the company’s first product submitted for FDA approval.
Stem Cells plans to enroll 16 participants in the current eye trial. Depending on the results, 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: 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.”