CT SPOTLIGHT

PVD Induction for Diabetic Eyes

Allegro goes beyond VEGF in investigating DME treatments.

ANDREW E. MATHIS, PhD, MANAGING EDITOR

Allegro Ophthalmics, LLC (San Juan Capistrano, CA), is currently enrolling a trial of its integrin peptide inhibitor Luminate (internally known as ALG-1001) to induce posterior vitreous detachment in patients with nonproliferative diabetic retinopathy. The phase 2 study, which will eventually enroll 125 patients in one of four arms (three Luminate arms of different doses and a control arm), will seek to determine whether the drug can induce a PVD of at least stage 3. Retinal Physician discussed the trial with Vicken Karageozian, MD, president and chief medical officer at Allegro.

The rationale for inducing a PVD in a diabetic eye centers on reducing the levels of VEGF in contact with the retina. “The vitreous acts like a big drug depot,” Dr. Karageozian explains. “When the retina produces VEGF, it accumulates in the vitreous. We know from studies in vitrectomized patients, as well as in patients with age-related PVD induction, that removal or breakdown of the vitreous is correlated with much better natural history in these patients because you don’t have a gel sitting right there in front of the retina accumulating VEGF.”

Dr. Karageozian cites data showing a rate of progression to vision-threatening disease of 35% in diabetic retinopathy patients without a PVD vs 5% in patients with a PVD. In this study among 403 patients, Ono et al found that complete PVD proved a strong negative risk factor for diabetic retinopathy. “There are three reasons why this might be so,” Dr. Karageozian says. “First, breakdown of the jelly into liquid allows it to diffuse the VEGF out of the eye; second, the gel is no longer able to act as a scaffold for vessels to grow on; and third, anterior-chamber fluid flows into the retina, increasing oxygen levels and prohibiting production of VEGF.”

Luminate is also being studied in a phase 2 trial in patients with diabetic macular edema (DME). That trial, which seeks to enroll 150 patients to compare three doses of Luminate to focal laser and bevacizumab (Avastin, Genentech, South San Francisco, CA) arms, is evaluating Luminate as a treatment for DME. However, Dr. Karageozian says that Luminate might ultimately be valuable for preventing progression in patients with diabetic retinopathy—almost like a vaccine—in addition to treating patients whose retinopathy has already progressed to DME.

“The challenge with existing treatments is that you have to wait until the condition is serious before you can treat the patient,” Dr. Karageozian says. Based on the theory that, if a diabetic eye can be treated earlier rather than later, a greater recovery of visual acuity is likely, earlier treatment with Luminate might result in better long-term VA outcomes. “If you administer Luminate before there are signs of vision loss, then it can be used before the patient’s vision gets really bad,” he adds.

The PVD trial is more than half enrolled. Nonproliferative diabetic retinopathy patients with no PVD or PVD of stage 1 or 2 can enroll if they are at least 45 years old and have controlled intraocular pressure. More information can be found at the ClinicalTrials.gov Web site: https://clinicaltrials.gov/ct2/show/NCT02435862. RP