Early trial shows application of RXi’s skin-scar drug in wet AMD

Eight of the study's nine patients showed improvements in best corrected visual acuity after at least seven months. (Pixabay)

RXi Pharmaceuticals unveiled positive safety and efficacy results in an early-phase study of its antifibrotic agent RXI-109 in patients with advanced neovascular age-related macular degeneration, demonstrating improvements in visual acuity and no drug-related adverse events across escalating doses.

An RNA interference-based therapeutic, RXI-109 is designed to inhibit multiple pathways linked to fibrosis, including scar formation in the skin. The Marlborough, Massachusetts-based company is also studying the drug in cutaneous warts, as well as hypertrophic and keloidal scars.

In the open-label phase 1/2 trial—the first exploring its use as an ocular injection against retinal scarring linked to wet AMD, which affects about 10% of AMD patients in the U.S.—RXi sequentially enrolled nine patients in three cohorts at increasing doses.

The study met its primary objective with no dose-limiting toxicities and no indications of inflammation or other tolerability issues, the company said in a statement. Five patients reported events related to the intraocular injection procedure. Each participant received four doses in one eye by intravitreal injection at one-month intervals, followed by a four-month observation period. In total, 25 adverse events were reported, which the company described as mild or moderate.

Eight of the nine patients showed improved best corrected visual acuity in their treated eye compared to their first examination, while one had a lower score, for a median improvement of 32%.

In addition, imaging and analysis suggested “a halt or even reversal of the disease progression in the study eye of several subjects,” the company said. Central lesion thickness shrank by 6.9% on average, with a greater change seen in the highest-dose group, with an average of 10.2%.

"This study is exciting on several levels,” RXi Chief Development Officer Gerrit Dispersyn, M.D., said in a statement. “First, the impressive safety and tolerability of intravitreal injections of RXI-109 and the promising clinical data, support further development of this compound in retinal scarring. In addition, these positive findings also open significant avenues for the use of our platform technology in ophthalmology, with sd-rxRNA targeting other proteins for other ocular indications.”

“Also, the results contribute to an already extensive set of data that RXI-109, by preventing the overexpression of connective tissue growth factor, can result in a positive impact in various indications where excessive fibrosis is seen,” Dispersyn added. The dosing information will be used to plan a future phase 2 study, and RXi said it is actively seeking partners to outlicense both its dermatology and ophthalmology franchises.