RXi Pharmaceuticals this week released data from a phase I trial of its dermal anti-scarring drug RXI-109, showing that the compound was safe and well-tolerated.
The company also said that it has added additional cohorts to the study, which is expected to wrap up by year end, and broke out details from its plan to advance RXI-109 into later-stage clinical studies in the fourth quarter.
RXI-109 comprises siRNAs designed to inhibit connective tissue growth factor, or CTGF, a protein linked to wound healing and other fibrotic processes. It employs the company's proprietary self-delivering technology, which enables cellular uptake without the need for a delivery vehicle.
In the phase I trial, nine healthy volunteers received eight 2-centimeter skin incisions on their abdomen. Four of the incisions were treated with three intradermal doses of RXI-109, ranging from 1.25 mg/cm to 3.75 mg/cm, and four with placebo injections, all over a two-week period. The subjects were monitored for safety, as well as local and systemic side effects, over 84 days.
According to RXi, RXI-109 was well tolerated by all volunteers, and dose-dependent silencing of CTGF mRNA was observed with a “more pronounced effect” of 43 percent silencing at the higher doses tested. Importantly, the drug did not appear to slow wound healing, and no subject developed abnormal scars.
During a webcast investor and analyst meeting held this week, RXi’s Chief Development Officer Pam Pavco noted that the company has added two cohorts to the phase I study in order to “explore different dosing options.” The trial is now set to wrap up before the end of the year.
Release of the new phase I data comes about one month after RXi announced that a phase I trial testing single doses of RXI-109, ranging from 0.5 mg/cm to 5 mg/cm, in healthy volunteers (GSN 6/6/2013). As in the second phase I, treatment was well tolerated and did not impair wound healing.
Based on these data, RXi is preparing to move RXI-109 into three phase IIa studies that will evaluate the drug in patients, Pavco said during her presentation.
Two of the trials will focus on lower abdominal scarring, which she said makes sense for the company because “we’ve already looked at scarring on the abdominal skin, so it was a way to keep in the same area.”
The first study will enroll women who have a poor scar-related outcome following Caesarean section or partial hysterectomy, and the second will focus on women who have scars following breast surgeries.
Each is expected to enroll about 50 patients who will undergo scar-revision surgery and then be treated with RXI-109 on one side of their abdomen and placebo on the other, allowing for in-patient controls.
The primary endpoint will be an assessment of the drug’s clinical effect after three months by a direct comparison of scarring on treated and untreated areas of the skin, with second endpoints including safety, determination of optimal dosing, and clinical effects at six and nine months after scar-revision surgery.
The principle investigators in the study, which is expected to take place at around five to eight sites, will be plastic surgeons or specialized dermatological surgeons, Pavco noted.
One of these studies is slated to begin in the fourth quarter, with the second starting early next year.
The third planned phase IIa study will examine RXI-109 in patients undergoing surgery for the removal of earlobe keloids — a scarring side effect of ear piercing in keloid-prone individuals.
As in the other trials, patients will be treated on one ear with RXI-109 and with placebo on the other. The primary objective is the assessment of a clinical effect at three months via direct comparison of the surgical areas, with safety and optimal dosing as secondary objectives.
This study is slated to enroll between 10 to 20 patients, with RXi deciding whether to expand the trial once data becomes available, Pavco said. It is set to kick off in the fourth quarter.
Though it is primarily focused on RXI-109 in dermal scarring, RXi continues to see promise for the agent in ocular conditions, namely those associated with retinal scarring given its association with CTGF.
Further, Pavco pointed out that much of the pre-investigational new drug application toxicology studies RXi ran for RXI-109 in skin scarring overlap with those required for these ophthalmological indications.
“We’ll have to do some [additional] toxicology where we look at the ocular toxicity of RXI-109 … but it’s not a full-blown program,” she said. “We’ve already done a lot of what needs to be done, so we feel like we can move into these areas fairly quickly.”
First up in this area is proliferative vitreal retinopathy, a condition caused by the buildup of scar tissue on the retina following surgery to correct a detached retina. The company is currently working with collaborators at the University of California, Santa Barbara, who are testing self-delivering RNAi molecules in a rat model of retinal detachment-associated scarring, Pavco said.
Also in ophthalmology, RXi is pursuing retinoblastoma, a rare cancer that originates in the retina and typically affects young children.
This disease is “driven by mutations in the RB1 gene, but there are a lot of other … genes that are also involved and support the cancer’s growth,” she stated. “Our goal is to look at several of these novel genes and … be able to block the growth of the cancer.”
To date, RXi has to date achieved dose-dependent silencing of target mRNA in retinoblastoma cell lines, and has shown uptake of its RNAi molecules into human retinoblastoma cells in a mouse model.
The company also continues to explore the possibility of resurrecting Opko Health’s one-time phase III wet age-related macular degeneration drug bevasiranib, which RXi acquired this year (
The company did not provide any timelines for its ocular disease programs.