RXi Pharmaceuticals Announces Pharmacokinetic Results of its Single Dose Phase 1 Study with RXI-109 in Healthy Volunteers
Results show limited systemic exposure, supporting the excellent safety profile of this intradermally injected drug in humans
WESTBOROUGH, Mass.--(BUSINESS WIRE)--Nov 15, 2012 - RXi Pharmaceuticals Corporation (OTC: RXII), a biotechnology company focused on discovering, developing and commercializing innovative therapies addressing major unmet medical needs using RNA-targeted technologies, today announced the pharmacokinetic results of their single dose Phase 1 study with RXI-109 in healthy subjects. This drug candidate is a highly selective CTGF targeting sd-rxRNA® compound that is administered through intradermal injections to prevent or reduce dermal scarring following surgery or trauma, as well as for the management of hypertrophic scars and keloids.
In this study, 15 volunteers divided over 5 cohorts received single intradermal injections in a dose escalating manner, and blood was drawn at various time points to evaluate the distribution of the drug beyond the injected tissue, into the systemic circulation. Previous primate toxicology work with RXI-109 had shown that the peak blood levels obtained after intradermal injections with 10 mg/kg were approximately 3.5% of the peak levels obtained after intravenous injections with the same dose. With the different doses in the primate study, the dermal and systemic side effects in the animals were minimal. The maximum dose administered intradermally in the human subjects was on average only 0.3 mg/kg at the highest dose, i.e., more than 30 times lower than the dose given to the primates. The calculated relative systemic exposure in the 15 volunteers was between 1 and 7% (mean 5%), which is very similar to the systemic exposure in primates. As reported earlier, the drug was very well tolerated in all volunteers tested.
"These data confirm our first clinical observations, that subjects had no significant side effects or complaints after intradermal injection with RXI-109," said Dr. Geert Cauwenbergh, President and CEO of RXi Pharmaceuticals. He added that, "Considering the absence of toxicity in our primate toxicology studies at much higher doses, given both intradermally and intravenously, and considering the very similar low degree of systemic exposure we have found in our volunteers, we are confident in moving forward into a multiple dose Phase 1 study in the very near future. The subjects from our first study with RXI-109 are currently in the process of undergoing their abdominoplasty, which will provide samples that will allow us to also make a clinical and histological evaluation of single dose RXI-109 treatment versus placebo in these subjects."
With cosmetic surgical procedures becoming increasingly more common to improve appearance, or to correct skin imperfections as a result of trauma or disease, scarring has become a much more significant side effect of such interventions. In humans, scarring of the skin after surgery, trauma, or burns can cause debilitating aesthetic, functional and psychological effects. Particularly problematic are raised or hypertrophic scars and keloids, scars which extend beyond the original skin injury. Medical treatment for scarring remains limited. Often with severe scarring, acceptable treatment plans include scar revision surgery which may alter the scar initially, but may also result in further exacerbation of the surgically-intervened area. Such exacerbation of a scar can often be a debilitating and painful experience for the patient and, to date, there are no FDA-approved therapeutics for the treatment of post-operative scars. RXI-109 has been shown in cell culture and animal models to reduce CTGF, a growth factor that is essential in the wound healing cascade. Elevated levels of CTGF-dependent signaling can prolong the tissue repair process and lead to pathological scarring.
RXi Pharmaceuticals first clinical program centers around RXI-109, a self-delivering RNAi compound (sd-rxRNA) developed by RXi for the reduction of dermal scarring in planned surgeries. RXI-109 is designed to reduce the expression of CTGF (connective tissue growth factor), a critical regulator of several biological pathways involved in fibrosis, including scar formation in the skin. The first clinical trial of RXI-109, initiated in June 2012, will evaluate the safety and tolerability of several dose levels of RXI-109 in humans and may provide preliminary evidence of surgical scar reduction. As there are currently no FDA-approved drugs to prevent scar formation, a therapeutic of this type could have great benefit for trauma and surgical patients (especially relating to raised or hypertrophic scarring), as a treatment during the surgical revision of existing unsatisfactory scars, and in the treatment, removal and inhibition of keloids (scars which extend beyond the original skin injury).
RXi's sd-rxRNA compounds 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. They are hybrid oligonucleotide molecules that combine the beneficial properties of both conventional RNAi and antisense technologies. The sd-rxRNAs have a single-stranded phosphorothioate region, a short duplex region, and contain a variety of nuclease-stabilizing and lipophilic chemical modifications. The combination of these features has been shown in vitro and in animal tissues, to allow sd-rxRNAs to achieve efficient spontaneous cellular uptake and potent, long-lasting intracellular activity.
About RXi Pharmaceuticals Corporation
RXi Pharmaceuticals Corporation (OTC: RXII) is a biotechnology company focused on discovering, developing and commercializing innovative therapies based on its proprietary, next-generation RNAi platform. Therapeutics that use RNA interference, or “RNAi,” have great promise because of their ability to “silence,” or down-regulate, the expression of a specific gene that may be over-expressed in a disease condition. 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, which targets CTGF (connective tissue growth factor), entered into a human clinical trial in June 2012 to evaluate its safety, tolerability and potential efficacy for scar prevention. For more information, please visit 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 future expectations, plan and future development of RXi Pharmaceuticals Corporation's products and technologies. These forward-looking statements about future expectations, plans and prospects of the development of RXi's products and technologies involve significant risks, uncertainties and assumptions, including the risk that RXi may not be able to successfully develop its candidates, the risk that the development of our RNAi-based therapeutics may be delayed or may not proceed as planned and we may not be able to complete development of any RNAi-based product, the risk that the development process for our product candidates may be delayed, risks related to development and commercialization of products by our competitors, risks related to our ability to control the timing and terms of collaborations with third parties and the possibility that other companies or organizations may assert patent rights that prevent us from developing our products. Actual results may differ materially from those contemplated by these forward-looking statements. RXi does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this release.
Contact: RXi Pharmaceuticals Corporation
Tamara McGrillen, 508-929-3646
Posted: November 2012