By Ed Susman
DENVER – An investigative drug aimed at preventing or reducing surgical scars appears to lower levels of a key component of scarring, according to early human studies presented at the 72nd annual meeting of the American Academy of Dermatology.
The drug, known now as RXI-109, is injected into the skin at the time of surgery and appears to dramatically reduce levels of connective tissue growth factor, says Lyn Libertine, MD, vice president for medical affairs at RXi Pharmaceuticals, the company developing the new agent.
“There are currently no drugs approved to prevent hypertrophic scar or keloid,” Libertine says. In oral poster presentations, Libertine and co-author Pamela Pavco, PhD, chief development officer at RXi, located in Westborough, Mass, reported that treatment in healthy volunteers indicates that the agent is successful in targeting connective tissue growth factor (CTFG).
In one study, eight incisions of 2 centimeters were made in the abdomen of 15 subjects. The incisions were spaced 4 cm apart. Three patients in each of five cohorts were injected with either placebo or RXI-109. On one side or the other, the active action was injected three times. Safety assessments were made throughout the 3-month study.
In the dose-ranging trial, subjects were injected with 10 mg, 20 mg, 30 mg, or 40 mg, she says. In a fifth cohort patients were delayed dosing until 2 weeks after the incisions were made, but that did not appear to have a positive impact on CTGF silencing. There was no significant difference in levels of CTGF at the 10 mg dose. When the 20 mg, 30 mg, and 40 mg cohorts were pooled, the decrease in CTFG was 45% compared to the side of the wound, which was injected with placebo (p=0.002).
The injections did not appear to cause any harm, Libertine says. “No negative effect on healing in healthy volunteers with no predisposition for bad scarring was observed,” she says.
In a second study, the incision procedure was repeated in healthy patients. This time, Pavco says, the researchers made the incisions in the pannus, and the tissue was examined after the patients underwent planned abdominoplasty.
The histology of the removed tissue demonstrated that the scarred area appeared to be smaller among the patients treated with RXI-109. In this study, the CTGF protein levels were about 85% of the levels in the scar where a placebo was administered (p=0.0044), Pavco said.
The results indicate a dose-dependent effect on CTGF silencing—an effect that is more pronounced at the higher dosing levels.
Libertine says the findings in the studies appear to mirror what was expected from the drug in these first-in-man trials. She says the results were encouraging enough for the company to initiate Phase 2 studies.