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According to Robert S. Kirsner, MD, PhD, of the University of Miami, and colleagues, the mean reduction in wound area at 12 weeks ranged from 8% to 16% greater with the mix of keratinocytes and fibroblasts versus placebo (P=0.0446), 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 (P=0.0267).
Kirsner stated that, “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.” “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 2.0% 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% 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 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 (0.5 x 106 to 5.0 x 106 cells every 7 or 14 days) or to a vehicle 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 (0.5 x 106 cells every 14 days) demonstrated the greatest efficacy, with an average reduction in wound size of 91% versus 80% 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% in the control groups versus 70% in patients who received 0.5 x 106 cells every 14 days (P=0.0267). 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 (P=0.0211). Comparison of healing rates showed that patients treated with the most effective dose of the spray-on cells had an 83% greater likelihood of wound healing compared with the patients who received vehicle only (P=0.0212).
Adverse event rates did not differ significantly across treatment groups. The only events that occurred in more than 5% of patients were new skin ulcers and cellulitis.
Kirsner RS, et al “Spray-applied cell therapy with human allogenic fibroblasts and keratinocytes for the treatment of chronic venous leg ulcers: A phase II, multicenter, double-blind, randomized, placebo-controlled trial” Lancet 2012; DOI: 10.1016/S140-6736(12)60644-8. |
