MARLBOROUGH, Mass.—RXi Pharmaceuticals Corporation, a biotechnology company focused on discovering, developing and commercializing innovative therapies addressing major unmet medical needs using RNA-targeted technologies, has announced completion of enrollment in its first Phase 2a study, RXI-109-1301. The preliminary results from the three-month observations confirmed the one-month findings that were reported in September of this year:
When treatment with RXI-109 was initiated two-weeks post-scar revision surgery, blinded evaluators were able to identify accurately the RXI-109-treated site at the three-month follow up more frequently (54 percent) than when treatment was initiated immediately post-scar revision surgery (24 percent).
These data provide guidance that dosing with RXI-109 during the proliferation phase provides a better outcome than dosing during the acute inflammatory phase of the wound healing process.
The results support the company's decision, for the ongoing Phase 2a studies, to start treatment two-weeks post-scar revision surgery (at the end of the acute inflammation phase), and explore extension of the treatment during the weeks of the proliferation phase (the period in the wound healing process during which hypertrophic scars can develop).
Based on these observations, the treatment regimens for the ongoing studies for revised keloids and scars, RXI-109-1401 and 1402 respectively, will be altered to optimize the timing and duration of dosing for RXI-109 in these indications.
"We are pleased to see that our early observations at 1-month post scar revision surgery reported in September are confirmed by our 3-month observations," said Dr. Geert Cauwenbergh president and CEO of RXI Pharmaceuticals. He added that, "Our work is obviously not done. The observations in RXI-109-1301 in our target population with hypertrophic scars allow us to fine tune the treatment schedules in the ongoing adaptive protocols. Keeping in mind that the duration of hyperproliferation is extended for hypertrophic scars and keloids, we can adjust the treatment length to accommodate for that variability factor."
RXi Pharmaceuticals' first clinical program involves RXI‑109, an sd-rxRNA® compound, developed for the reduction of dermal scar formation. RXI‑109 is designed to reduce the expression of connective tissue growth factor (CTGF), a critical regulator of biological pathways involved in fibrosis, including scar formation in the skin. The first clinical trials with RXI‑109 (RXI-109-1201 and RXI-109-1202) showed excellent safety and tolerability with ascending single and multiple doses, as well as dose-dependent effects on the CTGF protein and on the mRNA that controls production of this protein.
In November 2013, the company started its first Phase 2a study (RXI-109-1301) in patients who had pre-existing hypertrophic scars present on their lower abdomen for at least one year. In that study, the patients undergo scar revision surgery, after which they are treated with RXI-109 on one end of the scar and placebo on the opposite end of the scar. This study is ongoing but has completed enrollment. In April of this year, the company began its second Phase 2a study (RXI-109-1401) for RXI-109 treatment to prevent recurrence of keloids in patients undergoing keloidectomy (removal of keloid). Patients with two keloids of similar size and location are eligible for the study. After keloidectomy, the lesions are closed and one is treated with RXI-109, and the other is treated with placebo. As is the case for the study in hypertrophic scars, patients will be followed for several months (clinically and with photographs) after the end of treatment.
The company's third Phase 2a study (RXI-109-1402) was initiated in July 2014 for RXI-109 for the reduction of recurrence of hypertrophic scars following elective scar revision surgery. In this study, patients with either one long hypertrophic scar, or two scars comparable in length, anatomical location and characteristics, are eligible to receive scar revision surgery.
For a single scar, a portion of the revised scar segment will be treated with RXI-109 and a comparably sized length on the opposite end of the excised scar segment will be left untreated. If two scars are revised, one revised scar segment will be treated with RXI-109 and one scar will be left untreated after revision surgery. This third Phase 2a study will follow patients for nine months. Investigator and independent reviewer assessments will be used to evaluate the effectiveness of RXI-109 in preventing scar formation. Reviewers will evaluate and compare the appearance of the revised areas after treatment with RXI-109 or when left untreated.
All three Phase 2a trials incorporate a within-subject comparison of revised sites treated with RXI-109 vs. control sites. This is a powerful study design because it decreases the potential impact of variability due to patient-to-patient healing characteristics.
RXi Pharmaceuticals Corporation is a biotechnology company focused on discovering, developing and commercializing innovative therapies based on its proprietary, self-delivering RNAi platform. Therapeutics that use RNA interference, or "RNAi," have great promise because of their ability to down-regulate the expression of specific genes that may be over-expressed in disease conditions. Building on the pioneering work of scientific founder and Nobel Laureate Dr. Craig Mello, a member of the RXi Scientific Advisory Board, RXi's first RNAi product candidate, RXI‑109, a self-delivering RNAi compound, entered into human clinical trials in June 2012 and is currently being evaluated in Phase 2 clinical trials to reduce the formation of dermal scars and keloids. RXI-109 is designed to reduce the expression of connective tissue growth factor (CTGF), a critical regulator of biological pathways involved in fibrosis, including scar formation in the skin. RXi's sd‑rxRNA oligonucleotides are designed for therapeutic use and have drug-like properties, such as high potency, target specificity, serum stability, reduced immune response activation, and efficient cellular uptake. These hybrid oligonucleotide molecules combine the beneficial properties of conventional RNAi and antisense technologies.