Extensive studies in animals and initial experience in human trials support interest in integrin peptide therapy as an emerging new class of treatment for vascular eye disease, according to Baruch Kuppermann, MD, PhD.
Irvine, CA-Extensive studies in animals and initial experience in human trials support interest in integrin peptide therapy as an emerging new class of treatment for vascular eye disease, according to Baruch Kuppermann, MD, PhD.
“Integrin peptide therapy works by a distinctly different mechanism of action than anti-vascular endothelial growth factor agents and appears to have the potential to be stand-alone treatment or complementary to the standard of care,” said Dr. Kuppermann, professor of ophthalmology and biomedical engineering, Gavin Herbert Eye Institute, University of California, Irvine.
“There is evidence of its safety and efficacy as monotherapy and combined with ranibizumab in animal models of neovascularization, and safety and initial efficacy was observed in a phase I study of patients with diabetic macular edema (DME). Further studies are under way,” he added.
The clinical DME study evaluated the investigational compound ALG-1001 (Allegro), a synthetic oligopeptide that inhibits integrin receptors implicated in the angiogenic cascade, posterior vitreous detachment (PVD), and vitreous liquefaction. It enrolled 15 patients with advanced DME who received a 2.5-mg dose by intravitreal injection once monthly for 3 months and were followed for 3 months off-treatment. Baseline best-corrected visual acuity (BCVA) averaged 20/200 and mean central macular thickness (CMT) on optical coherence tomography (OCT) was 519 µm.
At the end of the study, no patients had lost vision or showed increased CMT, and there were no serious treatment-related adverse events. Mean BCVA improved to 20/125 and mean CMT was reduced to 387 µm. However, the changes were accounted for by eight “responders” whose mean BCVA improved from 20/200 to 20/100 and mean CMT changed from 563 to 370 µm.
“All of the responders had at least a three-line gain in vision, whereas the non-responders experienced no change, and the functional improvements were compatible with the OCT data,” Dr. Kuppermann said.
The observed adverse events were mostly related to the injection and were minor and transient. They included a case of transient elevated IOP that resolved spontaneously and transient mild intraocular inflammation in two patients who were successfully treated with a steroid.
Among the non-responders, one patient had a transient reduction in vision at the end of the study, but vision returned to baseline after another injection.
PVD induction was also assessed in the DME study. Among 11 patients with no or partial PVD at baseline, six developed total PVD and three developed partial PVD.
Dr. Kuppermann is a consultant to Allegro.
For more articles in this issue of Ophthalmology Times eReport, click here.