Topline Results From Prospective, Double-masked, Placebo Controlled Phase 2 Clinical Study Evaluating Luminate® (ALG-1001) in Patients with Symptomatic Focal Vitreomacular Adhesion

Purpose : To investigate the safety and efficacy of Luminate (ALG-1001), a synthetic anti-angiogenic and vitreolytic oligopeptide, administered intravitreally in patients with focal vitreomacular adhesion (VMA) or vitreomacular traction (VMT)

Safety and Efficacy of Risuteganib in Intermediate Non-exudative Age-Related Macular Degeneration

Purpose : Risuteganib is a small synthetic peptide that regulates select integrin functions involved in the pathogenesis of dry age-related macular degeneration (AMD). This study evaluated the safety and efficay of risuteganib for the treatment of dry AMD. Methods : Randomized, double-masked, placebo-controlled Phase 2 study in eyes with intermediate dry AMD presenting with best-corrected visual acuity (BCVA) between 20/40-20/200 was conducted across multiple centers in the United States. Patients were randomized to receive either intravitreal 1.0mg risuteganib or sham injection at baseline. At week 16, patients in the risuteganib group received a second dose and the sham group crossed over and receive a single dose of 1.0mg risuteganib. The primary endpoint was the percentage of population with ≥ 8 letters BCVA gain from baseline to week 28 in 1.0mg risuteganib vs baseline to week 12 for sham. Results : Forty-five patients were enrolled in the study. At baseline, mean patient age was 78.8 and 75.9 years and mean baseline BCVA was 67.1 and 64.4 letters in the sham and risuteganib groups, respectively. The primary endpoint was met; 48% of patients in the risuteganib group at week 28 and 7% of patients in the sham group at week 12 gained > 8 letters from baseline (p=0.013). Of the risuteganib treated patients, 20% gained > 15 letters at week 28; no patients in the sham group at week 12 had this gain. On a post-hoc masked analysis by 2 independent reading centers, greater outer retinal and photoreceptor thickness and volume and smaller ellipsoid zone defect area in the central 1 mm zone at baseline were associated with increased BCVA response to risuteganib. Risuteganib demonstrated a good safety profile in this study. Conclusions : Risuteganib showed significant benefit over sham in patients with dry AMD with respect to proportion of patients gaining > 8 letters of BCVA from baseline. Furthermore, post hoc analysis provides preliminary insights into baseline anatomic features that may help to determine likelihood of BCVA response to risuteganib. These findings will be confirmed in an upcoming larger trial

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