- RXI-109 is a self-delivering RNAi (sd-rxRNA) compound that targets connective tissue growth factor (CTGF), a key regulator of fibrosis and scar formation, and plays a key role in tissue regeneration and repair.
- Study successfully meets primary effectiveness objective with statistically significant outcomes for improved visual appearance for RXI-109 treated scar over control.
- RXI-109 meets secondary objective as it was shown to be safe and well tolerated.
- The exploratory endpoint for patient reported outcomes resulted in 88% of the patients indicating that RXI-109 treated scar looked better over control.
MARLBOROUGH, Mass., Dec. 18, 2017 /PRNewswire/ -- RXi Pharmaceuticals Corporation (RXII) a clinical-stage company developing a new class of RNAi-based therapeutics today announced positive results with its lead clinical compound RXI-109 in a Phase 2 clinical trial. RXI-109-1402 is an open-label, multi-center, prospective, within-subject controlled study evaluating the effectiveness and safety of RXI-109 on the outcome of scar revision surgery for hypertrophic scars in healthy adults. The primary effectiveness objective was met as shown by a statistically significant improved visual appearance of revised scars after scar revision surgery and treatment with RXI-109 versus control, as assessed by the investigator. The full study results show that the product was safe and well tolerated for all dosage groups. Exploratory endpoint analysis furthermore shows that the cosmetic outcomes of RXI-109 treated scars were highly preferred over the untreated revised scars, by both investigators and patients.
Joseph P. Hunstad, MD, FACSA, member of the Board of Directors for the American Society for Aesthetic Plastic Surgery and a Principal Investigator for the Company's Dermatology Clinical Program with RXI-109 stated that: "Today, scarring represents a high unmet medical need and based on our results; I believe that RXI-109 offers a clinically meaningful benefit for the treatment and prevention of hypertrophic scars following scar revision surgery. I look forward to providing further guidance in the development of this exciting new treatment option."
RXi's Chief Development Officer, Gerrit Dispersyn, Dr. Med. Sc., commented: "These results are very exciting, as they provide us with strong evidence that RXI-109, by preventing the overexpression of connective tissue growth factor, can result in a positive impact on the prevention of hypertrophic scars. The robustness of the data is shown by the fact that the effect of RXI-109 was significant by using both validated detailed scoring techniques, as well as simple qualitative assessments, and by the investigator driven data being further corroborated by an analysis of patient preferences. The fact that RXI-109 resulted in statistically significant improvements on scar outcomes at all follow-up time points for one of the dose groups, show that the effect of RXI-109 is both observed early on, and lasts at least throughout the entire follow-up time frame. In this study, we collected a lot of information that will allow us to perform additional analyses. Based on the current per protocol analysis, RXI-109 can be confidently moved to the next phase of clinical development."
Overall Efficacy Results
- Using the Investigator Scar Assessment Scale, which enables a structured clinical evaluation of scar quality, the difference between RXI-109 treated scars and untreated (control) scars, was statistically significant at all follow-up time points, for one of the treatment arms. The improvement over untreated scars was a mean 6.88 point change at 3 months (p=0.028), a mean 8.00 point change (p=0.013) at 6 months and a mean 7.53 point change (p=0.013) at 9 months post revision surgery. The Investigator Scar Assessment Scale is a validated scoring tool which accounts for several parameters including surface area, pliability, relief, thickness, pigmentation and vascularity.
- Using a qualitative measure of overall scar appearance (visual-analog-scale), the difference noted by the Investigator was also statistically significant for all follow-up time points, for the same treatment arm. The improvement over untreated scars was a mean 1.58 point change at 3 months (p=0.012), a mean 1.89 point change (p=0.004) at 6 months and a mean 1.55 point change (p=0.017) at 9 months post revision surgery.
- As an exploratory endpoint, patient reported outcome for scar ranking was evaluated. Patients were asked to answer which scar segment (A or B) looks 'better' or if they thought they were 'not different'. For the treatment arm mentioned above, 88% of the patients and 86% of the investigators preferred the RXI-109 treated scar.
Safety and tolerability
- Treatment with RXI-109 was well tolerated in treatment arms. There were no drug-related serious adverse events (SAEs) and most other treatment emergent adverse events (AEs) were those commonly found with intradermal injections, such as injection site pain (17.4%), and injection site erythema (11.8%).
Additional details from the Phase 2 study will be submitted for presentation at a future scientific conference.
Approximately 42 million surgeries occur in the United States alone each year.1 The American Society of Plastic Surgeons state that more than 170,000 patients receive scar revision therapy annually.2 Based on these populations, with costs primarily shouldered by patients, given the non-life-threatening nature of these indications, the resulting market potential could be worth as much as $1.5 billion. Given the current cost for cosmetic therapies such as Botox® and the fact that there are currently no approved treatment options for the prevention of hypertrophic scarring, premium pricing could be achieved with significant market penetration. Based on the study results, we are one step closer to having RXI-109 become the first solution for the prevention of hypertrophic scar formation in patients undergoing surgery or traumatic injury.
RXI-109 and RXi's sd-rxRNA technology platform are broadly protected in the United States and International regions. The Company's robust patent estate provides for multiple commercial and business development opportunities.
About Dr. Joseph Hunstad
Dr. Hunstad is one of the Principal Investigators for the Company's dermatology clinical program with RXI-109. His site has treated a large number of the subjects in the Company's clinical trials with RXI-109 to date. He received his Doctor of Medicine degree from the College of Human Medicine at Michigan State University and completed a General Surgery residency at Butterworth Hospital in Grand Rapids. He completed his Plastic Surgery residency at the Grand Rapids Area Medical Education Center, where he later served as Plastic Surgery Chief Resident for a year. He completed a Fellowship in Reconstructive Microsurgery at the MECOM Microsurgical Institute in Houston and is licensed to practice in North Carolina, Michigan, and Texas. Dr. Hunstad has been named one of the Best Plastic Surgeons in America by Castle Connolly, among numerous other awards and distinctions. Dr. Hunstad currently serves on the Board of Directors for the American Society for Aesthetic Plastic Surgery.
About RXi's self-delivering RNAi (sd-rxRNA) technology platform
sd-rxRNA, RXi's proprietary self-delivering RNAi platform, is a single chemically modified compound with delivery and therapeutic properties built directly into the compound itself. The compound is asymmetrical with a phosphorothioate backbone and contains chemical modifications that provide for efficient cellular uptake and gene silencing. These compounds are potent, stable and specific, and demonstrated to be safe and active in a clinical setting.
RXi's novel sd-rxRNA technology differs from natural and most synthetic RNA interference (RNAi) molecules in that they are chemically modified to allow for efficient internalization of the compounds by cells and silencing of the targeted genes. Importantly, unlike other naked siRNA compounds, delivery of sd-rxRNAs are not limited to a specific cell type. For local delivery and ex vivo cell-based therapeutic applications, our compounds do not require delivery vehicles. This is a major advantage, since delivery vehicles can have related toxicity that affects cell viability. sd-rxRNA has demonstrated nearly 100 percent transfection efficiency with high cell viability in numerous cell types.
About RXi Pharmaceuticals
RXi Pharmaceuticals Corporation (RXII) is a clinical-stage company developing innovative therapeutics that address significant unmet medical needs. Building on the pioneering discovery of RNAi, scientists at RXi have harnessed the naturally occurring RNAi process which can be used to "silence" or down-regulate the expression of a specific gene that may be overexpressed in a disease condition. RXi developed a robust RNAi therapeutic platform, including self-delivering RNA (sd-rxRNA®) compounds, that have the ability to highly selectively block the expression of any target in the genome, thus providing applicability to many therapeutic areas. Our current programs include dermatology, ophthalmology, and cell-based immunotherapy. RXi's extensive patent portfolio provides for multiple product and business development opportunities across a broad spectrum of therapeutic areas, and we actively pursue research collaborations, partnering and out-licensing opportunities with academia and pharmaceutical companies. For additional information, visit the Company's website, www.rxipharma.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about: our ability to successfully develop RXI-109, Samcyprone™ and our other product candidates (collectively "our product candidates"); the future success of our clinical trials with our product candidates; the timing for the commencement and completion of clinical trials; our ability to enter into strategic partnerships and the future success of these strategic partnerships; and our ability to deploy our sd-rxRNA® technology through partnerships, as well as the prospects of these partnerships to provide positive returns. Forward-looking statements about expectations and development plans of RXi's product candidates and partnerships involve significant risks and uncertainties, including the following: risks that we may not be able to successfully develop and commercialize our product candidates; risks that product development and clinical studies may be delayed, not proceed as planned and/or be subject to significant cost over-runs; risks related to the development and commercialization of products by competitors; risks related to our ability to control the timing and terms of collaborations with third parties; and risks that other companies or organizations may assert patent rights preventing us from developing or commercializing our product candidates. Additional risks are detailed in our most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q under the caption "Risk Factors." Readers are urged to review these risk factors and to not act in reliance on any forward-looking statements, as actual results may differ from those contemplated by our forward-looking statements. RXi does not undertake to update forward-looking statements to reflect a change in its views, events or circumstances that occur after the date of this release.
1 Sund B. New Developments in Wound Care. PJB Publications; London: 2000. pp. 1–255.