VIENNA — Integrin inhibitor risuteganib was effective in complementing the anti-VEGF pathway when administered sequentially to an anti-VEGF drug in patients with diabetic macular edema, according to the results of the DEL MAR phase 2b trial.
“Positive results were driven by patients who responded poorly to anti-VEGF therapy, exactly the patients who need the most help,” Pravin Dugel, MD, said at the Euretina meeting.
Integrins are cell surface receptors that mediate cell-to-cell interaction with further downstream kinase signaling and are upregulated in times of oxidative stress, Dugel said. They are associated with several systemic disease including cancer and autoimmune diseases.
“Four isoforms of integrins are most important in ophthalmology, and risuteganib inhibits three of those isoforms,” Dugel said.
In the trial, the effects of sequential vs. combined Avastin (bevacizumab, Roche/Genentech) and Luminate (risuteganib, Allegro Ophthalmics) treatment were compared with bevacizumab monotherapy. Best results in terms of visual acuity were obtained in the sequential arm of the study, which involved a loading dose of bevacizumab followed by three risuteganib injections at weeks 1, 4 and 8. Visual acuity improved significantly over the course of treatment and continued to improve for a further 12 weeks, meeting the primary endpoint of the study.
“We can conclude that the integrin inhibitor pathway complements the anti-VEGF pathway when given sequentially,” Dugel said. “Sequential administration of this drug allows for an immediate anti-permeability effect driven by the anti-VEGF, followed by long-term reduction of oxidative stress.”
Phase 3 studies are currently planned in the U.S. and Europe.
Dugel P, et al. Randomized, prospective, double-masked, controlled phase 2b trial to evaluate the safety and efficacy of ALG-1001 (Luminate) in diabetic macular edema (DME). Presented at: Euretina; Sept. 20-23, 2018; Vienna.
Disclosure: Dugel reports he is a consultant to Allegro Ophthalmics, Allergan, Novartis, Alcon and Genentech.