A spray formulation of allogeneic neonatal keratinocytes and fibroblasts healed venous leg ulcers without the need for tissue engineering, according to study published recently in The Lancet.
Adult outpatients with at least three leg ulcers, venous reflux confirmed by Doppler ultrasonography and adequate arterial flow were randomly assigned to five groups: 5×106 cells/mL every 7 days or every 14 days, 0.5×106 cells/mL every 7 days or every 14 days or to vehicle alone every 7 days. At least one ulcer had to measure between 2 cm² to 12 cm² in area and had to persist for 6 to 104 weeks. The mean percentage in wound area at the end of 12 weeks was considered the primary endpoint.
During the 12 week treatment period, patients assigned to the cell group experienced greater reduction in wound area vs. vehicle alone, with patients in the 0.5×106 cells/mL every 14 days yielding a 16% greater reduction on average than vehicle. Mean reduction in wound area was 40% after one application of the 0.5×106 cells/mL every 14 days vs. 23% in the vehicle group, according to study results. Between 3 and 9 weeks, patients assigned to 0.5×106 cells/mL every 14 days has the highest proportion of closed wound, and at 12 weeks, mean wound area was reduced by 91%.
Researchers found new skin ulcers and cellulitis occurring in only 5% of patients. In all treatment groups, pain associated with the treated wound decreased steadily during the 12-week period.
“The treatment we tested in this study has the potential to vastly improve recovery times and overall recovery from leg ulcers, without the need for a skin graft,” Herbert Slade, MD, of Healthpoint Biotherapeutics, said in a press release. “This means not only that the patient doesn’t acquire a new wound where the graft is taken from, but also that the spray-on solution can be available as soon as required — skin grafts take a certain amount of time to prepare, which exposes the patient to further discomfort and risk of infection.”
In an accompanying commentary, Matthias Augustin, MD, of the University Medical Center Hamburg in Hamburg, Germany, and Wolfgang Vanscheidt, MD, of Paula-Modersohn-Platz 3 in Freiburg, Germany, 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. The benefits identified by Kirsner and colleagues could well be applicable in other chronic wounds such as ischemic and diabetic foot ulcers.”
For more information:
Kirsner RS, Marston WA, Snyder RJ, et al. Spray-applied cell therapy with human allogeneic fibroblasts and keratinocytes for the treatment of chronic venous leg ulcers a phase 2, multicenter, double-blind, randomized, placebo-controlled trial. Lancet. Aug. 3, 2012. [Epub before print]
Augustin M, Vanscheidt W. Chronic venous leg ulcers: the future of cell-based therapies. Lancet. Aug. 3, 2012. [Epub before print]
Disclosures: Slade is employed by Healthpoint and holds an adjunct academic appointment at the University of North Texas Health Science Center. Augustin and Vanscheidt had no relevant financial disclosures.