Top-line data from a Phase IIb study of a novel integrin peptide (ALG-1001) to treat diabetic macular edema (DME) has indicated encouraging visual acuity gains, including a reduction in central macular thickness (CMT) comparable to that observed with anti-VEGF therapy. The study, conducted in 136 patients with DME at centres across the US employs engineered peptides to target integrin receptors involved in cell signaling and regulation and in neovascularisation. The underlying mode of action aims to exploit vitreolytic and anti-angiogenic pathways to inhibit new blood vessel formation and slow or halt vascular leakage in order to maintain and restore vision.
The clinical trial study was designed to demonstrate non-inferiority of ALG-1001 to bevacizumab, with non-inferiority defined as less than or equal to a 3-letter difference in the mean change in BCVA at the 20 week time-point. The double-masked, multi-center, dose-ranging study included three ALG-1001 arms (1.0 mg, 2.0 mg, and 3.0 mg) treated with 3 monthly ALG-1001 loading injections, followed by 12 weeks off treatment, and a 1.25 mg bevacizumab arm of 6 monthly injections. The clinical data collected from the study showed the mean gain in BCVA was 5.2 letters for patients in the 1.0 mg ALG-1001 arm 12 weeks off ALG-1001 loading, compared to 7.0 letters for patients in the 1.25 mg bevacizumab arm dosed every 4 weeks. The secondary endpoint for the study was non-inferiority to bevacizumab, defined as less than or equal to a 30 µm difference in the mean change in CMT. At the 20-week time-point, patients in the 1.0 mg ALG-1001 arm showed a mean reduction of 77µm 12 weeks off ALG-1001 loading, versus 104µm in the 1.25 mg bevacizumab arm dosed every 4 weeks. The treatment appeared to be well-tolerated with no drug toxicity or intraocular inflammation noted.
Commenting on the results, Peter K. Kaiser, M.D., Chaney Family Endowed Chair in Ophthalmology Research and Professor of Ophthalmology, Cleveland Clinic Lerner College of Medicine, and a member of the sponsor’s (Allegro) Scientific Advisory Board stated, the “Phase 2 results appear to be very promising. With half the number of injections and a unique mechanism of action, [ALG-1001] has demonstrated non-inferiority to anti-VEGF injections and appears to be extremely well-tolerated. [ALG-1001]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.”