Allegro Ophthalmics, LLC (San Juan Capistrano, CA), said its unique integrin peptide therapy Luminate for retinal disease demonstrated a more durable response than an existing anti-VEGF drug in a 136-patient phase 2b clinical trial for DME and expects to enter a phase 3 trial within a year.

Allegro says Luminate, which was initially developed in collaboration with scientists at CalTech, is unique because it attacks the "machinery" that creates neovascularization directly, as well as the signaling of VEGF itself. By disrupting the process that creates the unwanted blood vessels, it becomes difficult for this process to regenerate and restart.

DEL MAR Study Highlights

The DEL MAR study — designed to highlight Luminate's durability and monotherapy treatment potential — met its primary and secondary endpoints, demonstrating encouraging visual acuity gains and reduction in central macular thickness (CMT) that were deemed equivalent to bevacizumab (Avastin) monotherapy. The company said the trial included a range of disease severity, including difficult-to-treat patients.

The gains were achieved with half the number of Luminate injections (compared to bevacizumab) and were recorded at 12 weeks following the final Luminate injection, the company said, showing the possibility of a major potential reduction in treatment burden.

However, other retina drugs showing a durable response are already into phase 3 trials, including Ophthotech's Fovista/anti-VEGF combination and Alcon's brolucizumab, both for wet AMD. In addition, Allergan's abicipar pegol (DARPin) has demonstrated a durable response of up to 12 weeks in the phase 2 PALM trial for DME.

The primary endpoint of the DEL MAR study was non-inferiority to bevacizumab (defined as?=3-letter difference) in mean change in BCVA at 20 weeks. The Luminate results were achieved after three injections and 12 weeks off treatment, compared to 6 bevacizumab injections given every 4 weeks. The data showed the mean gain in BCVA was 5.2 letters for patients in the 1.0 mg Luminate arm at 12 weeks off after initial Luminate loading, compared to 7.0 letters for patients in the 1.25 mg bevacizumab arm dosed every 4 weeks. The secondary endpoint was non-inferiority to bevacizumab (defined as =30 µm difference) in mean change in CMT as measured by OCT. At week 20, patients in the 1.0 mg Luminate arm showed a mean reduction of 77µm 12 weeks off Luminate loading versus 104µm in the 1.25 mg bevacizumab arm dosed every 4 weeks.

The controlled, double-masked, multi-center, dose-ranging study, which included three Luminate arms (1.0 mg, 2.0 mg, and 3.0 mg) treated with three monthly Luminate loading injections followed by 12 weeks off treatment, and a 1.25 mg bevacizumab arm of six monthly injections, also found that Luminate was well-tolerated with no drug toxicity or intraocular inflammation noted.

"These positive results continue to affirm the safety and efficacy of Luminate, and confirm its 12-week monotherapy durability," said Vicken Karageozian, MD, president and chief medical officer, Allegro Ophthalmics.

"The DEL MAR phase 2 results appear to be very promising," said Peter K. Kaiser, MD, professor of Ophthalmology, Cleveland Clinic Lerner College of Medicine, and member of Allegro's Scientific Advisory Board. "With half the number of injections and a unique mechanism of action, Luminate has demonstrated non-inferiority to anti-VEGF injections and appears to be extremely well-tolerated. Luminate may potentially provide physicians and DME patients with a completely new option that improves visual and anatomic outcomes while reducing the burden of intravitreal injections."

Luminate has also shown promise in a phase 2 study for the treatment of vitreomacular traction (VMT) and vitreomacular adhesion (VMA), which met its primary endpoint with 50% of eyes achieving VMT/VMA release by 90 days.