Novel integrin regulator a key for AMD treatment

October 17, 2019
Cheryl Guttman Krader, BS, Pharm

Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

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.”

Related: Focusing the battle against dry AMD 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.

Related: Intraoperative surgical methods key to AMD treatment Dry AMD study
In the double-masked phase II study, intermediate dry AMD patients were randomly assigned to receive intravitreal injections of risuteganib 1mg or sham. The primary endpoint was percentage of patients achieving a BCVA improvement of ≥8 ETDRS letters.

Dr. Kaiser noted that natural history studies show that in general, vision does not improve in this population.

“The threshold of eight letters was chosen because a five-letter change in this patient population would be considered noise,” he explained.

At the primary endpoint of the study, the percentage of patients achieving a ≥8 letter gain in BCVA was significantly higher in the risuteganib group than in the control group, 48% versus 7.1%.

Watch here: Dr. Kaiser discusses how risuteganib fared in a phase II trial in patients with intermediate nonexudative AMD

The results are sparking a buzz among physicians and researchers alike.

“I am excited by the initial results from this phase II study,” Dr. Kaiser noted. “Having a potential treatment that addresses the unmet need in intermediate dry AMD would be beneficial for our patients who are currently not receiving any treatment.”

Conclusion 
Dr. Kaiser concluded that integrin regulation “provides a promising new therapeutic target for researchers and clinicians who are looking for new approaches to the management of vitreoretinal disease.”

Read more AMD content here 

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