This article was reviewed by Peter K. Kaiser, MD
A phase II study investigating intravitreal injection of risuteganib (Allegro Ophthalmics) in patients with intermediate nonexudative age-related macular degeneration (AMD) met its primary efficacy endpoint and found that the novel agent was associated with excellent safety, said Peter K. Kaiser, MD.
“Risuteganib is a small synthetic peptide that acts to regulate select integrin functions that appear to be involved in the pathogenesis of dry AMD,” said Dr. Kaiser, Chaney Family Endowed Chair in Ophthalmology Research and professor of Ophthalmology, Cole Eye Institute, Cleveland Clinic, Cleveland, OH.
Dr. Kaiser noted that the efficacy results from the phase II study are supported by additionalfunctional endpoints that will be presented at future meetings.
“The safety of risuteganib in this study is consistent with the safety profile observed in more than 1,200 injections that have been given outside this study,” he said. “Currently, a larger study is being planned to confirm these phase II study findings.”
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Mechanism of action
Understanding the potential roleof risuteganib as a treatment for dry AMD comes from a review of disease pathogenesis.
Dr. Kaiser noted that the retinal pigment epithelial (RPE) cells receiving continuous exposure to light leads to oxidative stress.
“Oxidative stress in part causes buildup of toxic byproducts in theform of drusen formation, thickening of Bruchs membrane, activation of the complement system, and eventually degeneration of the RPE and photoreceptors,” Dr. Kaiser said. “The inability of AMD patients to control this oxidative stress is related to mitochondrial dysfunction leading to increased levels of reactive oxygen species and subsequently integrin receptor deposition on cell surfacesthat produces an amplification effect and ultimately the structural changes associated with dry AMD.”
Risuteganib regulates integrin function and has been shown in multiple preclinical studies to beanti-inflammatory via action on the complement 3 receptor and to reduce mitochondrial reactive oxygen species production, improve mitochondrial bioenergetics, prevent cellular apoptosis, and improvecell viability.