Topline results from a phase 2 study demonstrated that Allegro Ophthalmics' first-in-class anti-integrin candidate, Luminate, can help restore vision in diabetic macular edema (DME) patients being treated with anti-VEGF therapy. The drug may also help those with chronic disease who no longer respond to anti-VEGF treatment.
Administered as an intravitreal injection, Luminate (previously known as ALG-1001) is a synthetic oligopeptide that inhibits 4 integrin receptor sites involved in angiogenesis and vitreolysis. The targeted receptors have functions both upstream and downstream of the VEGF pathways and can be manipulated to prevent new vascular sprouts, inhibit existing neovascularization and reduce fluid.
When used as a stand-alone treatment following an initial bevacizumab injection, Luminate appears noninferior to anti-VEGF monotherapy.
The multicenter DEL MAR trial randomized 80 DME patients to 1 of 5 arms:
- Sequential therapy of Luminate 0.5 mg or 1.0 mg at weeks 1, 4, and 8, followed by 12 weeks off-treatment, given after a single treatment of 1.25 mg bevacizumab (week 0).
- Direct combination of Luminate 0.5 mg or 1.0 mg given with bevacizumab 1.25 mg at weeks 1, 4, and 8, and 12 weeks off treatment
- 5 monthly injections of 1.25 mg bevacizumab (control arm)
According to the data released, visual improvement was equivalent between the sequential bevacizumab + 1.0 mg Luminate and bevacizumab-only control arms at all time points, including during the 12-week off-treatment durability assessment.
At the end of follow-up (20 weeks), the 1.0 mg sequential combined group showed an average gain of 7.1 letters, compared with 6.7 letters gained by the bevacizumab control group.
In line with previous reports, no drug toxicity was observed and the treatment was well-tolerated.
“Positive results in DEL MAR Stages 1 and 2 continue to confirm Luminate’s safety and efficacy, and its 12-week durability in patients with DME,” said Vicken Karageozian, MD, Allegro’s president and chief medical officer. “What’s more, about 60% of those treated in the DEL MAR trial had been chronic anti-VEGF users, which suggests that Luminate, with its unique mechanism of action, may successfully treat more patients, including those who don’t respond to anti-VEGF.”
Ongoing trials are evaluating the peptide therapy for wet AMD, vitreomacular traction, posterior vitreous detachment and nonproliferative diabetic retinopathy.