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

Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2) : 12-month results from a randomised, double-masked, phase 3 trial

Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth.GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 μL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366.Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016-0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group.Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy.Iveric Bio, An Astellas Company

Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration : A Randomized Phase 2 Trial

Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration

To investigate whether multiple intravitreal doses of up to 2 mg of an antigen-binding fragment known as ranibizumab, derived from a humanized anti-vascular endothelial growth factor antibody, can be tolerated and are biologically active when injected using a dose-escalating strategy in eyes of patients with neovascular age-related macular degeneration (AMD). Open-label, 2-center, uncontrolled, randomized clinical study of 3 different dose-escalating regimens of ranibizumab. Thirty-two patients with primary or recurrent subfoveal choroidal neovascularization secondary to AMD were enrolled. Baseline best-corrected visual acuity (VA) in the study eye was from 20/40 to 20/640 (Snellen equivalent). Treatment regimens consisted of 5, 7, or 9 intravitreal injections of ranibizumab at 2- or 4-week intervals for 16 weeks, with escalating doses ranging from 0.3 to 2.0 mg. Patients were evaluated through day 140, 4 weeks after their last injection. Safety was assessed based on ocular and nonocular adverse events, changes in VA, changes in intraocular pressure (IOP), slit-lamp ocular examination, changes in lesion characteristics based on fluorescein angiography and color fundus photography, and the presence of anti-ranibizumab antibodies. Twenty-nine patients received an injection at baseline, and 27 patients completed the study through day 140. Results were similar across the 3 treatment groups. All patients experienced ocular adverse events, most of which were mild. The most common ocular adverse events were iridocyclitis (83%) and injection-site reactions (72%). Inflammation did not increase with repeated injections, despite the increasing ranibizumab doses. Transient mild IOP elevations were common after ranibizumab injection. No serum anti-ranibizumab antibodies were detected. Overall, median and mean VAs in the study eyes improved by day 140 in all 3 groups. Only 3 of the 27 patients lost significant vision. There was no significant lesion growth, and a decrease in area of leakage from choroidal neovascularization was detected through day 140. Multiple intravitreal injections of ranibizumab at escalating doses ranging from 0.3 to 2.0 mg were well tolerated and biologically active in eyes with neovascular AMD through 20 weeks. Mild transient ocular inflammation was the most common postinjection adverse event

The Potential Importance of Detection of Neovascular Age-Related Macular Degeneration When Visual Acuity Is Relatively Good

The advent of anti-vascular endothelial growth factor treatment has changed the prognosis for patients with neovascular age-related macular degeneration (nvAMD). The ability to stabilize or improve vision with these treatments is a major step in enabling patients to continue to function at the highest possible level. Many studies have demonstrated that the better the visual acuity (VA) is at the time of treatment initiation, the higher the likelihood that VA will be better during at least the following 2 years; as such, detection of nvAMD when VA is relatively good is important. Data on the VA of patients with intermediate AMD and VA at the time of nvAMD diagnosis suggest that patients are typically losing an average of 3 to 5 lines of vision and possibly more between the time that intermediate AMD progresses to nvAMD and the diagnosis of nvAMD is made. The average patient may have nvAMD for 6 to 12 months before diagnosis and treatment initiation. Current efforts in management of nvAMD are primarily aimed at optimizing anti-vascular endothelial growth factor treatments that have the potential to improve VA outcomes by a magnitude of letters. Additional tools or other efforts to identify patients with nvAMD before substantial vision loss has occurred may reduce the amount of visual loss sustained with anti-vascular endothelial growth factor therapy, and have the potential to improve VA outcomes substantially