Randomized, Prospective, Double-Masked, Controlled Phase 2b Trial to Evaluate the Safety & Efficacy of ALG-1001 (Luminate®) in Diabetic Macular Edema

Purpose : Currently, there is only one predominant treatment paradigm for diabetic macular edema (DME): anti-VEGF agent as first line, followed by corticosteroids as second line. We performed a double-masked, placebo-controlled, randomized multi-center phase 2b trial to evaluate the safety & efficacy of ALG-1001, a novel first-in-class integrin inhibitor, as compared to bevacizumab in DME. Methods : 80 subjects were randomly assigned to 5 treatment groups: 1.25mg bevacizumab control arm of 5 monthly injections (Group 1); single treatment of 1.25mg bevacizumab at week 0 followed by three ALG-1001 injections (1.0mg or 0.5mg) at weeks 1, 4 and 8 (Groups 2 & 3); ALG-1001 (1.0mg or 0.5mg) given in direct combination with bevacizumab 1.25mg at weeks 1, 4 and 8 (Groups 4 & 5). Efficacy outcomes were change from baseline in BCVA and OCT CMT at week 20. Results : 65 subjects were included in the per protocol population. Group 2 demonstrated the best efficacy among the ALG-1001 groups. Mean change in BCVA were 6.7 and 7.1 letters for 1.25mg bevacizumab and ALG-1001 1.0mg in sequential treatment, respectively. BCVA improved earlier than CMT improvements suggesting a new mechanism of action unlike anti-VEGF. There were no drug related SAEs in ALG-1001 groups. Conclusions : Primary endpoint of non-inferiority in BCVA was met with sequential dosing of a single bevacizumab treatment plus 3 doses of 1.0mg ALG-1001 vs 6 doses of 1.25 mg bevacizumab (≤3 letters difference) at week 20. ALG-1001 showed 12-week durability in all study subjects in sequential therapy arms