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 ranged from 8% to
16% greater with the mix of keratinocytes and fibroblasts versus placebo (P=0.0446),
according to Robert S. Kirsner, MD, PhD, 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 (P=0.0267).
Differences in healing rates emerged within a week after initial
treatment, they reported online in The Lancet.
"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 toldMedPage 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 2.0% 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 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 (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.
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, Matthias Augustin, MD, of
the University of Hamburg, and Wolfgang Vanscheidt, MD, 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."
Action Points
- Standard treatment of venous leg ulcers with infection control, primary dressings, and the application of high-strength compression results in healing in between 30% and 75% of cases, while the remainder of ulcers become chronic.
- This randomized study evaluated the effects of a spray-applied cell therapy containing growth-arrested allogeneic neonatal keratinocytes and fibroblasts.
- Note that the study results suggest that venous leg ulcers can be healed with the spray formulation.
Primary source: The Lancet
Source reference:
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.
Source reference:
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.
Additional source: The Lancet
Source reference:
Augustin M, Vanscheidt W "Chronic venous leg ulcers: The future of cell-based therapies" Lancet 2012; DOI: 10.1016/S0140-6736(12)61255-0.
Source reference:
Augustin M, Vanscheidt W "Chronic venous leg ulcers: The future of cell-based therapies" Lancet 2012; DOI: 10.1016/S0140-6736(12)61255-0.
By Charles Bankhead, Staff Writer, MedPage Today
Published: August 02, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Courtesy of MedPage Today
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