PolarityTE CSO on Harnessing Mother Nature’s Regenerative Power and Phase 3 Study in Diabetic Foot Ulcers.
Regenerative tissue developer PolarityTE recently received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) for its SkinTE product. SkinTE is derived from a patient’s own skin to regenerate a full-surface, functionally polarized skin with all its layers, including hair follicles and glands.
The public biotech is currently enrolling patients in a Phase 3 study for the treatment of diabetic foot ulcers, which occur in about 15 percent of people with diabetes and can lead to infection, hospitalization and lower extremity amputation.
Longevity.Technology: The FDA says that regenerative medicine therapy is a candidate for RMAT when it is intended to “treat, modify, reverse, or cure” a serious or life-threatening condition, and preliminary clinical evidence suggests that the therapy has the potential to address unmet medical needs for this disease. The new designation gives PolarityTE the opportunity to accelerate the advancement of its regenerative technology in the marketplace. To find out more, we spoke to Dr. Nikolai Sopko, PolarityTE’s Chief Scientific Officer and VP of R&D.
PolarityTE was founded in 2016 based on research by two resident physicians at Johns Hopkins Hospital. While early approaches to skin regeneration focused on one cell type or scaffold, Sopko says those approaches were limited.
“It’s rare to find diseases, especially non-genetic diseases, where there’s just one protein driving the disease,” he says. “As a rule, they are much more complex than we thought. And healing is the same.”
“In classic biotech research, the approach is to figure out what Mother Nature is doing, break it down, and then try to put it back together for your own purposes,” adds Sopko. “Everyone was focused on finding the holy grail — a specific cell type or protein that can drive a cure. But we now know that Mother Nature doesn’t work that way – she’s very redundant and uses many parallel paths.”
Use nature’s ability to regenerate
As it turns out, Mother Nature is already very good at performing the kind of regeneration that researchers have struggled for years to recover.
“On average, we get cut over 1,000 times in our lifetime, and 99% of the time we heal perfectly,” says Sopko. “But there are situations in life that our biology isn’t built for — car accidents, house fires, and the chronic wounds that come with old age.”
PolarityTE was founded to take systems already created by nature and optimize them for diseases and conditions for which we have not yet developed defenses.
“Evolutionary pressures on humans generally ease off after three to four decades after we’ve raised our children,” says Sopko. “And then we see a lot of these diseases of old age, because we didn’t really have to evolve to cope with living that long.”
The company’s approach is to harness our body’s natural regenerative abilities and encourage cells to create functional tissue. Its first product, SkinTE, being evaluated in randomized controlled trials, aims to regenerate the skin. SkinTE is an “autologous, heterogeneous skin construct” made from a small piece of a patient’s healthy skin at PolarityTE’s facility in Salt Lake City, Utah. It looks like a thick paste that is spread over the patient’s wound and contains multicellular segments that contain cells and extracellular matrix to promote natural wound healing.
“We are currently treating chronic wounds – diabetic foot ulcers, pressure ulcers and venous leg ulcers,” says Sopko. “These typically affect older people with chronic illnesses where our skin’s natural healing response is already overwhelmed.”
“When we have a wound, our body tries to close it from the outside in, but there’s a limit to how fast cells can grow and migrate inward. And with chronic wounds, even though they can be relatively small, the tissue is essentially biologically bankrupt, it’s just depleted.”
When SkinTE is taped into a wound, you are essentially getting a supply of “fresh troops” to allow your body’s natural defenses to kick into action.
“The new skin cells are healthy, activated and can contribute to the cell material,” says Sopko. “They can implant, multiply, and migrate into the wound bed, in addition to signaling to the other cells in your body to really start this wound healing process.”
The unique manufacturing process developed by PolarityTE also aims to ensure that any new skin cells introduced into a wound are “activated”.
“When you cut yourself, only the cells about 80 cells away from the injury are actually activated,” says Sopko. “One reason we can use such a small piece of skin from a patient is that we’re able to activate a large majority of the cells in that harvest, so they’re all primed and ready to go into this wound-healing mode.” And because we’re doing a full harvest, not just removing the top layer of skin, we can also treat a much larger wound area.”
Cooperation with the FDA
PolarityTE initially chose to commercialize regenerative tissue products through a lesser-known route with the FDA.
“We actually treated 1,200 patients and did some post-marketing studies to support safety and efficacy,” says Sopko. “But this path is typically for simpler products than ours, so we decided to phase out SkinTE and go down the more formal path for biologics licensing applications that we are now going through.”
Progress at the FDA was initially slow, largely due to the very new technology PolarityTE has developed.
“We are the first multicellular autologous biological drug on the market,” says Sopko. “The FDA has never seen a product like ours before, and understandably that brings new challenges. We need to help them understand what they are dealing with.”
One of the biggest challenges lies in manufacturing. Good manufacturing practice demonstrates that a biotech company is developing a product that is consistently pure and of good quality.
“When you’re dealing with a biologic like ours, that’s actually a really difficult aspect because our raw material comes from the patient,” says Sopko. “You don’t just buy ingredients in bulk from a pharmaceutical company and then package them. And so this process was quite challenging and quite fun. We had to develop many new assays, which the FDA had probably never seen before in this context, to show that we are activating the tissue, we have the right cell types and that the cells are viable.”
Phase 3 study ongoing
Luckily, PolarityTE was still able to leverage the clinical data from its previous studies, meaning the company could jump straight into pivotal phase 3 trials, starting with diabetic foot ulcers.
“We specifically targeted the intractable ones — more complex ulcers with exposed tendons, muscle, and bone,” says Sopko. “In these cases, the skin has a really hard time growing back and patients are at significant risk for infection, amputation and loss of that limb.”
All in all, this process took about a year, but PolarityTE got the green light in January of this year, and the first patient was enrolled in the study in April.
“We anticipate that the study will include a total of 100 patients who will be randomized one-to-one to standard of care versus SkinTE plus standard of care,” says Sopko. “We are essentially comparing other advanced wound treatments currently on the market to our product. It’s a challenging area — there haven’t been many studies of these heavier DFUs — we’re one of maybe two FDA-registered studies on this wound type at all.”
PolarityTE hopes to complete both the current pivotal Phase 3 study in diabetic foot ulcers and a subsequent Phase 3 study in more severe cases over the next year.
“We really want this product to work well in difficult situations,” says Sopko. “There are many good products for simpler wounds, but there are many patients in difficult situations who really don’t have many options. And we see that this product really stands out in these difficult situations.”