Spray-on skin cells significantly improved wound healing versus standard care in patients with venous leg ulcers, results of a randomized trial showed.
The mean reduction in wound area at 12 weeks was up to 16 percent greater with the mix of keratinocytes and fibroblasts compared to placebo, according to Dr. Robert S. Kirsner of the University of Miami, and colleagues. The best results occurred with the lowest dose of spray-on cells, which resulted in complete healing in almost a third more patients as compared with the placebo group.
Differences in healing rates emerged within a week after initial treatment, they reported online in The Lancet.
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"At this point of its evaluation, this product has superior healing and a faster time frame than anything else we've seen in the treatment of venous leg ulcers," Kirsner told MedPage Today. "That still remains to be proven in phase III studies, which have begun enrolling patients in the U.S. and will also be enrolling patients in Europe."
Chronic venous insufficiency in the legs leads to venous ulcers in 1.5 to 2 percent of adults 65 and older, the authors noted. Standard treatment consists of infection control, primary dressings, and application of high-strength compression, which leads to healing in 30 to 75 percent of cases.
In the remaining cases, chronic unresolved wounds develop, marked by persistent inflammation in the wound bed and dysfunctional fibroblasts and keratinocytes.
Skin autografts induce complete wound healing but create a residual wound at the donor site. Engineered skin allografts have achieved varying degrees of success, according to the background information.
Successful grafting with autologous and allogeneic keratinocytes in fibrin compounds suggests the cells and the products they release play a key role in healing, the authors continued.
The evidence provided a starting point for development of the spray-on cells, currently known as HP802-247. The product consists of cryopreserved fibroblasts and keratinocytes derived from neonatal foreskin, tissue that usually is discarded after circumcision of newborns. Thawed cells are suspended in a modified fibrin spray for application to a wound.
In vitro studies have shown that the optimized cellular formulation produces a variety of growth factors essential to tissue development.
Kirsner and colleagues evaluated the spray-on cellular compound in a randomized study involving patients with as many as three leg ulcers associated with sonography-confirmed venous reflux and inadequate arterial circulation. Investigators at 28 centers in North America randomized 228 patients to one of four doses of the spray-on cells or to a placebo.
Patients in both groups received standard wound care in addition to randomized therapy.
The primary endpoint was average reduction in wound area at 12 weeks. The lowest dose of HP802-247 demonstrated the greatest efficacy, with an average reduction in wound size of 91 percent versus 80 percent with standard care and placebo. The other three doses of the spray-on cells achieved mean reductions in wound area of 84% to 87%.
The proportion of patients who had complete healing by week 12 was 46 percent in the control groups versus 70 percent in patients who received cells every 14 days. The other active-therapy groups also had higher rates of complete healing compared with the control group, but the differences did not reach statistical significance.
The most effective dose of HP802-247 achieved wound closure in an average of 50 days versus 71 days in the control group. Comparison of healing rates showed that patients treated with the most effective dose of the spray-on cells had an 83 percent greater likelihood of wound healing compared with the patients who received vehicle only.
Adverse event rates did not differ significantly across treatment groups. The only events that occurred in more than 5 percent of patients were new skin ulcers and cellulitis.
The ability to specify a dose, frequency, and duration of treatment is a key distinguishing feature of the spray-on cells compared with other tissue-based treatments for venous leg ulcers, Dr. Matthias Augustin of the University of Hamburg and Dr. Wolfgang Vanscheidt of Dermatologische Praxisgemeinschafts in Freiberg, Germany wrote in an accompanying commentary.
The costly nature of tissue-based therapies requires careful evaluation to determine the most cost-effective use of the therapies.
"The questions of which products best promote healing and which products fail to increase healing rates of previously nonhealing ulcers need to be answered and are essential to address cost-effectiveness," they wrote.
"In these wounds, prolonged futile, conservative treatment will increase costs without additional benefit. Therefore, the temporary higher costs for additional cell and tissue-engineered therapy can be justified as an investment in improved healing."