Arcion Therapeutics, a venture backed clinical stage biotechnology company developing topical therapies for chronic pain, today announced top-line results from a successful Phase 2b double-blind, randomized, placebo-controlled clinical trial of its lead topical pain candidate, ARC-4558, in adult patients with painful diabetic neuropathy (PDN). Arcion recently held an End of Phase 2 meeting with the United States Food and Drug Administration (FDA) and the ARC-4558 program is now poised to enter Phase 3 studies. ARC-4558 is a 0.1% gel formulation of clonidine hydrochloride for topical administration.
The study results successfully demonstrated therapeutic potential for treating PDN with ARC-4558 by targeting abnormal nerve signaling at the level of the skin with a 0.1% topical gel formulation of clonidine. ARC-4558 was most effective in reducing pain in subjects with evidence of preserved nociceptors (nerve fibers responsible for pain signaling) in the skin. In subjects with at least minimal nociceptor function, ARC-4558 was significantly more effective in reducing pain than placebo (p<0.05). The significance of the response increased with higher levels of nociceptors in the subject's skin (p<0.005). ARC-4558 did not demonstrate efficacy in subjects lacking evidence of preserved nociceptor function.
The ITT (intent to treat) population was comprised of a mix of subjects in which about half had little or no nociceptor preservation and therefore the pooled results were not significant. Plasma levels of clonidine were consistently low or undetectable. No serious or severe adverse events were attributable to ARC-4558 treatment and the topical formulation was well-tolerated at the site of skin application.
"The top-line data reported today for ARC-4558 provide strong support for Arcion's fundamental approach of applying therapies topically to relieve neuropathic pain by targeting nerve signaling at the level of the skin," said James Campbell, M.D., President and CEO of Arcion. "Through this study, we identified a simple, predictive clinical test to identify non-responders to ARC-4558, which should enable us to optimize subject enrollment in future studies. Based on our successful End of Phase 2 meeting with the FDA, we believe ARC-4558 will be the first PDN treatment indicated to treat patients who have demonstrable functional nociceptors in the skin. The full Phase 2b results will be submitted for future peer review and we look forward to advancing the ARC-4558 program in Phase 3 studies."
Michael C. Rowbotham, M.D., Adjunct Professor of Neurology and Anesthesia and Director, UCSF Pain Clinical Research Center, commented, "Painful diabetic neuropathy is frequently a debilitating condition that severely impacts a patient's quality of life and ability to carry out normal day-to-day functions. There are approved therapies to control the pain, but issues of tolerability and efficacy seriously limit their usefulness. A novel mechanism-based topical treatment with a low liability of systemic side effects has promise to advance significantly the treatment of this condition and improve the quality of life for a large number of patients."
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