|
 Mr. Ferguson |
The treatment currently generating the most interest is Juvista, a scar-reduction treatment the active pharmaceutical ingredient of which, human transforming growth factor beta-3 (TGFß3), has been shown in phase II trials to reduce scars when injected directly into the wound. As often is the case, the researchers stumbled upon TGFß3 accidentally while studying something else — cleft lips.
"We were doing experiments on alligator embryos in which we cut the lips to make a surgical model of cleft lip," relates Mark Ferguson, Renovo's CEO. "What we found, however, was that the wound healed perfectly with no scar, and that discovery of scar-free embryonic wound healing in animals was of profound scientific interest."
UNDER INVESTIGATION The researchers went on to investigate what was different between embryonic wounds that would heal without a scar and adult wounds that do scar. They discovered that TGFß3 was a key regulator in scar-free embryonic healing, with levels of the molecule being high in the embryo and low in adults.Further research showed that adding TGFß3 to the adult wound by injecting it into the wound margins and the dermis of the skin caused the wounds to heal with notably decreased scarring.
Preclinical adult in vivo models showed injection of TGFß3 "reduces early extracellular matrix deposition and these molecules are deposited with a markedly improved architecture in the neodermis, resembling that of normal skin." Seven phase II, double-blind, placebo-controlled clinical trials with more than 1,500 patients have been conducted and have demonstrated both the compound's safe administration and statistically and clinically significant improvement in scar appearance.
Trials to determine the best dosing regime have meanwhile found that the drug works better if injected directly through the skin at the time of wounding and again 24 hours after.
DIVERSE RESULTS The studies have included subjects ranging in age from 19 to 94, with wide-ranging skin types, Mr. Ferguson explains.
"The studies have included a preponderance of Caucasians, but there have also been a range of Africans, Indians, people from Arabian cultures and other backgrounds, and when we finish our program, there will be the appropriate balance of skin types."
Results suggest that the drug seems to work even better on darker skin types, and trials are underway to determine if Juvista can help prevent keloid formation.
"There were snippets of evidence from some patients in our clinical trials indicating that the drug may prevent keloid formation, so we have a pilot study under way," Mr. Ferguson tells Cosmetic Surgery Times.
Another potentially exciting indication for Juvista is scar revision, which involves cutting out an existing scar, then treating the new wound with Juvista injections.
A trial in which scar revision wounds were treated on one end with Juvista and the other end with a placebo showed statistically significant improvement on the Juvista-treated end as far as 12 months out, which was the duration of the study.
"What is exciting about scar revision is these are people who are really troubled about their scars and we've shown a very clear beneficial effect of the drug in those cases," Mr. Ferguson says.
While Juvista trials continue in the U.S., Renovo has been working with regulators in Europe and is planning final phase III trials on the indication of scar revision surgery in the second half of 2008. After that, the FDA will be their next stop.
Most scar prevention methods available to surgeons offer ho-hum results, so hopes are high that Juvista might offer something better, states Tom Mustoe, M.D., professor of surgery and chief of the Division of Plastic and Reconstructive Surgery at Northwestern University.
