Article Date: 3/1/2012

Going to the Source
CLINICAL TRIAL SPOTLIGHT

Going to the Source

Integrin peptide therapy shows early promise in the treatment of vascular eye disease.

Andrew E. Mathis, PhD, MEDICAL EDITOR

The big breakthrough in retina that was made several years ago was the discovery that compounds able to bind to vascular endothelial growth factor can stop and even reverse damage to the macula caused by exudative age-related macular de generation, and in more recent years several studies have been undertaken to test the efficacy of anti-VEGF drugs in diabetic macular edema.

But what about stopping the production of VEGF in the first place? A new start-up biotechnology company, Allegro Ophthalmics of San Juan Capistrano, believes it can do just that, and it’s betting on its ALG-1001 compound to do it. This approach, called integrin peptide therapy, has shown promise in preclinical and phase 1 studies. Hugo Quiroz Mercado, MD, who is a principal investigator on Allegro’s trials for ALG-1001, spoke to Retinal Physician about the drug.

WORKING UPSTREAM

Dr. Quiroz-Mercado explained that the mechanism of action of ALG-1001 has the same target as drugs like Lucentis, but that it works else-where in the VEGF pathway. “ALG-1001 works upstream to shut off VEGF production,” he says. “By targeting VEGF production at the endothelial cells and VEGF effects at different levels of the affected tissues, ALG-101 may produce a more durable and ‘potent effect’ on tissues like the retina and retinal pigment epithelium.”

However, ALG-1001’s mechanism is not focused solely at the level of production of VEGF. Dr. Quiroz-Mercado adds, “ALG-1001 acts at different levels inside the endothelial cells, as opposed to current antiangiogenic therapy, which ‘inactivates’ some amounts of VEGF that is released by endothelial cells. Furthermore, by inducing vitreous liquefaction, ALG-1001 increases VEGF turnover.” It also targets tyrosine kinase, which plays a key role in the downstream activation of VEGF receptors, thereby inhibiting angiogenesis and decreasing inflammation.

DATA THUS FAR

The results that Allegro has seen so far with ALG-1001 are promising. “In rabbit studies, we did not observe toxicity, either on light microscopy or electron microscopy,” Dr. Quiroz-Mercado notes. “We were able to demonstrate production of vitreous liquefaction and induction of posterior vitreous detachment.” The latter process is helpful in delaying the progress of DME and diabetic retinopathy.

ALG-1001 also received a nice boost in October of last year when data from Allegro’s phase 1 study of ALG-1001 for DME were presented at the AAO meeting in Chicago. The study showed that eight of the 15 patients who were enrolled in the trial demonstrated three to five lines of BCVA improvement after 90 days, as well as definitive improvement in central retinal thickness as measured by OCT. Those patients who did not respond to treatment did not experience any disease progression during the trial. In addition, the clinical benefit lasted until the end of the trial, equating to 90 days of treatment.

ON THE HORIZON

Currently, Allegro is undertaking a phase 1/2 study of ALG-1001 in DME. Dr. Quiroz-Mercado, who is an investigator on this study, said, “This is a collaborative study with the Association for the Prevention of Blindness in Mexico City. We are currently enrolling diabetic patients with macular edema.” While safety and efficacy are the primary end points being measured with this trial, a secondary outcome measurement of improvement in ETDRS BCVA is also being examined, as well as a reduction in central macular thickness on OCT.

In addition, a phase 2 trial of the drug in wet AMD is planned for this year, and that study will enroll 75 subjects in the United States. Readers interested in more information can contact Allegro at (949) 940-8130 or via e-mail at info@allegroeye.com. And keep an eye on our Clinical Trials Update section for the full trial info. RP



Retinal Physician, Volume: 9 , Issue: March 2012, page(s): 70