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The first drug in the new class integrin peptide therapy continues to show continued efficacy and safety in various clinical trials.
Take-home message: The first drug in the new class integrin peptide therapy continues to show continued efficacy and safety in various clinical trials.
By Vanessa Caceres; Reviewed by Hugo Quiroz-Mercado, MD
Denver-A variety of clinical trials are showing efficacy and safety for the use of (Luminate [previously known as ALG-1001], Allegro Ophthalmics) for wet age-related macular degeneration (AMD), as well as other retinal diseases, said Hugo Quiroz-Mercado, MD.
“It’s been differentiated from anti-vascular endothelial growth factor (VEGF) therapy, because it has a different mechanism of action in which it both regresses and inhibits vascularization,” said Dr. Quiroz-Mercado, professor and director of ophthalmology, Denver Health Medical Center, University of Colorado.
The first-in-class, anti-integrin peptide drug approaches vitreoretinal diseases with two distinct mechanisms of action: anti-angiogenesis and vitreolysis. The drug interferes with the construction of new blood vessels, as well as the vitreoretinal interface, according to Dr. Quiroz-Mercado.
This is in contrast with anti-VEGF therapy, which slows the growth of blood vessels.
So far, the integrin peptide therapy has been studied in wet AMD, diabetic macular edema (DME), vitreomacular traction (VMT), and posterior vitreous detachment (PVD) for diabetic retinopathy, Dr. Quiroz-Mercado said.
In clinical trials with more than 350 intravitreal human injections to date, the medication had a solid safety and clinical profile for all of the aforementioned conditions. These studies have found a consistent durability of 3 to 4 months, best-corrected visual acuity (BCVA) improvements similar to that as anti-VEGF levels, and a response in some patients who had plateaued or no longer responded to anti-VEGF therapy, he said.
Phase I DME Study. Results from a phase I DME study with the drug showed no patients lost vision, adverse events were mild and usually injection-related, and there were a mean peak BCVA improvement of 11 letters. Eight patients improved three to five lines (Figure 1).
Improvements lasted 3 and sometimes 4 months off-treatment, Dr. Quiroz-Mercado said.
There was a mean peak central macular thickness improvement of 31% as seen via optical coherence tomography (OCT) in the study. That improvement typically held until study day 150-3 months off-treatment.
Phase Ib/IIa Wet AMD Study. Dr. Quiroz-Mercado also presented the results of a phase Ib/IIa, 6-month, dose-ranging study in wet AMD. Patients received three injections of the drug as monotherapy and 4 months off-treatment follow-up.
Seven of seven subjects receiving a 3.2-mg dose improved to a peak benefit of five letters in BCVA measured at 4 months after treatment, he noted. There were no serious adverse events.
Phase IIb DME/PVD Study. Dr. Quiroz-Mercado shared information on a phase IIb DME/PVD trial that began October 2014 for the integrin peptide therapy. The study builds on the phase I DME trial and replicates the dosage, formulation, and dosing schedule.
In the randomized, controlled, double-masked new study, 150 subjects are separated into five study arms. Efficacy endpoints are OCT central subfield thickness and BCVA improvements versus bevacizumab (Avastin, Genentech) or focal laser.
Increased durability of effect with participants using the medication as a monotherapy is a secondary endpoint of the study. Researchers are assessing how participants are faring at 3 and 4 months off-medication.
Other Phase II Studies. Currently, several phase II studies with the integrin peptide therapy in DME and vitreomacular traction (VMT) are ongoing.
In addition, a recently cleared phase II clinical trial for PVD for diabetic retinopathy is anticipated to begin mid-2015, Dr. Quiroz-Mercado said.
Hugo Quiroz-Mercado, MD
This article was adapted from Dr. Quiroz-Mercado’s presentation during Retina Subspecialty Day at the 2014 meeting of the American Academy of Ophthalmology. Dr. Quiroz-Mercado did not indicate any proprietary interest in the subject matter.