THE LATEST PUBLISHED RESEARCH
Welcome to Review of Ophthalmology's Retina Online newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible report to keep you up to date on important information affecting the care of patients with vitreoretinal disease.
Archway Randomized Phase III Trial Paves the Way for Susvimo Approval
Genentech’s Port Delivery System with ranibizumab was recently approved in the United States for the treatment of neovascular age-related macular degeneration, and was given the new brand name of Susvimo. The approval was based on the data from the Phase III, open-label, randomized Archway study. Here’s a look at the study’s findings.
Patients with nAMD diagnosed within nine months of screening previously treated with and responsive to anti-vascular endothelial growth factor therapy were included. They were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/mL with fixed 24-week refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every four weeks (monthly ranibizumab).
The primary endpoint was change in best-corrected visual acuity score from baseline averaged over weeks 36 and 40 (NI margin, -4.5 Early Treatment Diabetic Retinopathy Study letters; equivalence margin, ±4.5 ETDRS letters).
Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 (PDS Q24W) and 75.5 (monthly ranibizumab) ETDRS letters (Snellen equivalent 20/32). Adjusted mean (standard error) change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 (0.5) ETDRS letters in the PDS Q24W arm and +0.5 (0.6) in the monthly ranibizumab arm (difference, -0.3; CI, -1.7 to 1.1). Here are some of the findings:
• The PDS Q24W was noninferior and equivalent to monthly ranibizumab.
• Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4 percent) didn’t receive supplemental ranibizumab treatment before the first refill-exchange procedure, including four patients who discontinued treatment before the first refill-exchange procedure.
• Prespecified ocular adverse events of special interest (AESIs) were reported in 47 (19 percent) PDS Q24W and 10 (6 percent) monthly ranibizumab patients.
• Ocular AESIs in PDS-treated patients included four (1.6 percent) endophthalmitis cases, two (0.8 percent) retinal detachments, 13 (5.2 percent) vitreous hemorrhages, six (2.4 percent) conjunctival erosions and five (2 percent) conjunctival retractions.
• Most ocular adverse events in PDS patients occurred within one month of implantation.
Investigators wrote that PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab with 98.4 percent of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.
SOURCE: Holekamp NM, Campochiaro PA, Chang M, et al. Archway randomized phase 3 trial of the port delivery system with ranibizumab for neovascular age-related macular degeneration. Ophthalmology 2021; Sep 28. [Epub ahead of print].
Biosimilar SB11 vs. Reference Ranibizumab in nAMD
Researchers provided longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration, as part of a randomized, double-masked, parallel-group, Phase III equivalence study.
The patient population was patients who were at least 50 years old with nAMD (n=705); one eye of each patient was studied. The intervention was 1:1 randomization to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures included visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks.
Here are some of the findings:
• Baseline and disease characteristics were comparable between treatment groups.
• Of 705 randomized participants (SB11: n=351; RBZ: n=354), 634 participants (89.9 percent; SB11: n=307; RBZ: n=327) completed the study until week 52.
• Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ.
• The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was -0.6 letters (CI, -2.1 to 0.9) and of change from baseline in central subfield thickness was -14.9 µm (CI, -25.3 to -4.5).
• The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32 percent vs. RBZ: 29.7 percent) and serious ocular TEAE (SB11: 2.9 percent vs. RBZ: 2.3 percent) appeared comparable between treatment groups, and no new safety concerns were observed.
• The PK and immunogenicity profiles were comparable, with a 4.2 percent and 5.5 percent cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively.
Researchers found that the findings further support the biosimilarity established between SB11 and RBZ.
SOURCE: Bressler NM, Veith M, Hamouz J, et al. Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes. Br J Ophthalmol 2021 Oct 16. [Epub ahead of print].
Outcomes of Patients with Submacular Hemorrhage Secondary to AMD in the IVAN Trial
Researchers compared demographics, visual acuity and retinal morphology between those with and without baseline submacular hemorrhage (SMH) for patients enrolled in the Inhibit VEGF in Age-related Choroidal Neovascularization trial (IVAN).
The secondary analyses of RCT image and clinical data included clinical trial data collected in 23 UK hospitals of IVAN study eyes (with untreated neovascular age-related macular degeneration (at randomization) with at least 12 months’ follow-up and adequate imaging.
Study eyes were randomly assigned to monthly ranibizumab, as-needed ranibizumab, monthly bevacizumab or as-needed bevacizumab. Imaging at baseline graded independently for presence, type, position and extent of SMH. Main outcome measures included visual acuity (primary outcome), subretinal fibrosis, atrophic scarring, and retinal thickness outcomes at 12 and 24 months
A total of 535 of 605 IVAN trial participants were included. Here are some of the findings:
• Patients with SMH at baseline (286, 53 percent) were older (p=0.010), and affected eyes were more likely to have intraretinal fluid present (p=0.038).
• VA was significantly worse in those with baseline SMH at month zero (p<0.001; estimate of difference: six letters with 95 percent confidence intervals of four to eight letters), but the difference decreased and wasn’t significant at month 12 or 24.
• No significant association was found between baseline SMH and subretinal fibrosis, atrophic scarring or central retinal thickness.
Researchers determined that presence of SMH at baseline was associated with age, intraretinal fluid and reduced baseline VA, although VA was no longer significantly different by month 12.
SOURCE: Mehta A, Steel DH, Muldrew A, et al. Associations and outcomes of patients with submacular haemorrhage secondary to age-related macular degeneration in the IVAN trial. Am J Ophthalmol 2021; Oct 5. [Epub ahead of print].
Real-world Outcomes & Treatment Patterns in Patients Treated with Anti-VEGF for nAMD in Sweden
Investigators analyzed and compared the number and interval of anti-vascular endothelial growth factor injections in neovascular age-related macular degeneration patients, as well as visual development in patients followed up for one to three years in clinical practice and during different index periods.
The observational study included treatment-naïve eyes with nAMD from the Swedish Macula Register that started treatment between 2007 and 2017. The eyes were stratified by different index periods (2007 to 2010; 2011 to 2013; 2014 to 2015; and 2016 to 2017) and by follow-up cohorts for each index period of one, two or three years (cohorts 1 to 3). Their intravitreal anti-VEGF treatment was assessed by number of injections, injection intervals, visual acuity and near VA change.
Here are some of the findings:
• From the earliest index period (2007 to 2010) to the latest (2016 to 2017), the number of injections increased for the comparable follow-up time: 6.2 ±1.4 vs. 8.3 ±2 injections after year one, 4.8 ±1.6 vs. 6.7 ±2.4 during year two.
• The last injection interval was 73 ±34 days after one, 71 ±33 after two, and 67 ±32 after three years of follow-up for the index period 2014 to 2015.
• For the same period, the percentage of eyes with at least two consecutive 12- to 16-week injection intervals over one-, two- and three-year follow-up increased 5.2 percent, 15 percent and 17.5 percent, respectively.
• Baseline VA for eyes indexed 2016 to 2017 increased and presented with 62.1 ±13.4 letters compared with 57.7 ±13.5 letters in 2007 to 2010; p<0.0001.
Investigators reported, from the earliest to the latest index periods, the number of injections increased for the comparable follow-up time. At the same time, they wrote, baseline and near VA, and outcomes improved continuously.
SOURCE: Schroeder M, Westborg I, Fluur C, et al. Exploration of real-world outcomes and treatment patterns in patients treated with anti-vascular endothelial growth factors for neovascular age-related macular degeneration in Sweden. Acta Ophthalmol 2021; Sep 20. [Epub ahead of print].
Occurrence of Rare Variants in Complement Factor H Gene in Early-onset Drusen Maculopathy
Early-onset drusen maculopathy (EODM) is a severe disease and can lead to advanced macular degeneration early in life; however, genetic and phenotypic characteristics of individuals with EODM are not well-studied, according to researchers. They aimed to identify genotypic and phenotypic characteristics of individuals with EODM.
This case-control study collected data from the European Genetic Database from September 2004 to October 2019. A total of 89 patients with EODM diagnosed at 55 years or younger, and 91 patients with age-related macular degeneration diagnosed at 65 years or older were included.
Coding regions of CFH, CFI, C3, C9, CFB, ABCA4, PRPH2, TIMP3 and CTNNA1 genes were sequenced, genetic risk scores were calculated based on 52 AMD-associated variants and phenotypic characteristics on color fundus photographs were analyzed comparing patients with EODM and AMD.
Main outcomes and measures included genetic risk scores, frequency of rare genetic complement variants, and phenotypic characteristics.
This case-control study included 89 patients with EODM (mean age, 51.8 ±8.7 years; 58 ±65.2 percent were female) and 91 patients with AMD (mean age, 77.6 ±6.1 years; 45 [49.5 percent] were female).
• At a mean age of 56.4 ±7.3 years, 40 of 89 patients with EODM (44.9 percent) were affected by geographic atrophy or choroidal neovascularization.
• A lower GRS was observed in patients with EODM compared with patients with AMD (1.03 vs. 1.60; p=0.002), and 27 of 89 patients with EODM (30.3 percent) carried rare variants in the CFH gene compared with seven of 91 patients with AMD (7.7 percent).
• Carriership of a rare CFH variant was associated with EODM (OR, 7.2; CI, 2.7 to 19.6; p<0.001).
• A large macular drusen area (more than half-covered with drusen) was observed in patients with EODM (24 of 162 eyes [14.8 percent]) compared with patients with AMD (nine of 164 eyes [5.5 percent]) (OR, 4.57; CI, 1.5 to 14.1; p=0.008).
Researchers determined that a large proportion of patients with EODM in the study carried rare CFH variants, with most of the identified CFH variants clustered in the first seven complement control protein domains affecting factor H and factor H-like 1. Because EODM frequently leads to advanced macular degeneration at an early age and can result in many years of vision loss, they wrote that the study supports targeting the complement system and sequencing the CFH gene in patients with EODM to improve genetic counseling and future treatments for AMD.
SOURCE: de Breuk A, Heesterbeek TJ, Bakker B, et al. Evaluating the occurrence of rare variants in the complement factor H gene in patients with early-onset drusen maculopathy. JAMA Ophthalmol 2021; Oct 14. [Epub ahead of print].
Six-year Incidence of AMD & Correlation to OCT-derived Drusen Volume
Scientists reported the six-year incidence of optical coherence tomography-derived age-related changes in drusen volume and related systemic and ocular associations.
Chinese adults ages 40 years and older were assessed at baseline and six years with color fundus photography (CFP) and spectral-domain optical coherence tomography. CFPs were graded for AMD features, and drusen volume was generated using commercially available automated software.
A total of 4,172 eyes of 2,580 participants (mean age: 58.12 ±9.03 years; 51.12 percent women) had baseline and six-year follow-up CFP for grading. Of these, 2,130 eyes of 1,305 participants had gradable SD-OCT images, available for analysis. Here are some of the findings:
• Based on CFP grading, 136 participants (3.39 percent) developed incident early AMD and 10 (0.25 percent) developed late AMD. Concurrently, retinal pigment epithelial-Bruch's membrane (RPE-BrC) volumes decreased, remained stable and increased in 6.8 percent, 78.5 percent and 14.7 percent, respectively, over six years.
• Having eyes with RPE-BrC volumes >0 mm3 at baseline was associated with twofold higher prevalence rate of any AMD at baseline (p<0.001).
• Multivariable analysis showed that, in comparison to eyes in which RPE-BrC volume was unchanged, volume decrease was significantly associated with older age (OR=1.30; p<0.001), smoking (OR=2.21; p=0.001) and chronic kidney disease (OR=3.4, p=0.008), while an increase was associated with older age (OR=1.36; p<0.001) and hypertension (OR=1.43; p=0.016).
Scientists concluded that AMD incidence detected at six years on CFP had a low correlation to OCT-derived drusen volume measurement change. They added that older age and some systemic risk factors were associated with drusen volume change, providing new insights into the relationship between systemic risk factors and outer retinal morphology in Asian eyes.
SOURCE: Tan AC, Chee ML, Fenner BJ, et al. Six-year incidence of age-related macular degeneration and correlation to OCT-derived drusen volume measurements in a Chinese population. Br J Ophthalmol 2021; Oct 4. [Epub ahead of print].
Choroidal Vascularity Index Association & GA Progression
Investigators assessed the correlation between choroidal vascularity index (CVI) and the enlargement of geographic atrophy lesions secondary to age-related macular degeneration during two-year follow-up.
In this longitudinal observational study, 26 eyes (26 patients, mean age 75.7 ±8.8 years) affected by GA were included. CVI was calculated in the subfoveal 3,000-μm area. The main outcome measure included correlation analysis between baseline CVI and the rate of GA enlargement.
Here are some of the findings:
• During the two-year follow-up, mean GA area increased between the first and second year from 6.99 ±5.28mm2 to 10.69 ±6.61 mm2 (p<0.001), respectively, accounting for a growth rate of 0.35 ±0.20 and 0.31 ±0.17 mm/year after the square root transformation.
• Stromal choroidal area (SCA) significantly decreased during the two-year follow-up (p=0.002).
• A significant correlation was found between baseline CVI and rate of GA enlargement (r=-0.432, p=0.027), and between SCA and rate of GA enlargement (r=0.422, p=0.032).
• No other significant relationship was found among choroidal parameters with the rate of GA enlargement.
Investigators wrote that CVI impairment was related to the rate of enlargement during the one-year and two-year follow-up in patients affected by GA. As such, they added, CVI could be considered a predictor of GA progression in the clinical setting, and as a new potential biomarker in the efficacy evaluation of new GA interventions.
SOURCE: Sacconi R, Battista M, Borrelli E, et al. Choroidal vascularity index is associated with geographic atrophy progression. Retina 2021; Sep 17. [Epub ahead of print].
Assessing Reading Performance in GA Secondary to AMD with Visual Function and Structural Biomarkers
Researchers prospectively evaluated reading performance in geographic atrophy and assessed its association with established visual function assessments and structural biomarkers.
The noninterventional, prospective natural history study (Directional Spread in Geographic Atrophy) included patients with geographic atrophy secondary to AMD recruited at the University Hospital in Bonn, Germany. Participants were enrolled from June 2013 to June 2016. Analysis began December 2019 and ended January 2021.
Reading acuity and reading speed were assessed using Radner charts. Longitudinal fundus autofluorescence and infrared reflectance images were semi-automatically annotated for geographic atrophy, followed by extraction of shape-descriptive variables. Linear mixed-effects models were applied to investigate the association of the variables with reading performance.
A total of 150 eyes of 85 participants were included in this study (median [IQR] age, 77.9 [72.4 to 82.1] years; 51 women [60 percent]; 34 men [40 percent]). Here are some of the findings:
• Reading performance was impaired, with a median (IQR) monocular reading acuity of 0.9 (0.4 to 1.3) logarithm of the reading acuity determination and a reading speed of 52.8 (zero to 123) words per minute.
• In the multivariable cross-sectional analysis, best-corrected visual acuity, area of geographic atrophy in the central Early Treatment Diabetic Retinopathy Study subfield, classification of non-center vs. center-involving geographic atrophy, and area of geographic atrophy in the inner-right ETDRS subfield showed strongest associations with reading acuity (cross-validated R2 for reading acuity=0.69).
• Regarding reading speed, the most relevant variables were best-corrected visual acuity, low-luminance visual acuity; and area of geographic atrophy in the central ETDRS subfield, in the inner-right ETDRS subfield and in the inner-upper ETDRS subfield (R2 for reading speed=0.67).
• In the longitudinal analysis, a similar prediction accuracy for reading performance was determined (R2 for reading acuity=0.73; R2 for reading speed=0.70).
• Prediction accuracy didn’t improve when follow-up time was added as an independent variable.
• Binocular reading performance didn’t differ from reading performance in the better-seeing eye.
Researchers concluded that the association of reading acuity and speed with visual functional and structural biomarkers supported the validity of reading performance as a meaningful endpoint in clinical trials. These findings suggested that measures in clinical and low-vision care for patients with geographic atrophy should focus primarily on the better-seeing eye.
SOURCE: Künzel SH, Lindner M, Sassen J, et al. Association of reading performance in geographic atrophy secondary to age-related macular degeneration with visual function and structural biomarkers. JAMA Ophthalmol 2021; Sept 30. [Epub ahead of print].
Temporal Variation of OCT Biomarkers as Predictors of Anti-VEGF Treatment Outcomes in DME
Scientists reported a longitudinal analysis of specific optical coherence tomography features in eyes with diabetic macular edema-treated with anti-VEGF.
A total of 133 eyes of 103 consecutive patients with center-involving DME were included in the study. The eyes were treated between August 2008 and April 2019, with three monthly intravitreal anti-VEGF injections—with or without prompt or deferred laser—followed by pro re nata (PRN) retreatment. The following OCT biomarkers were evaluated:
• subfoveal neuroretinal detachment (SND) (defined as present [SND+] or absent [SND-]);
• hyperreflective retinal foci (HRF) number (defined as: absent/few [HRF-] or moderate/many [HRF+]);
• external limiting membrane (ELM) integrity;
• central macular thickness (CMT); and
• central retinal thickness (CRT).
The researchers evaluated changes in SND status and in the number of HRF at each DME recurrence throughout the follow-up period. They also assessed mutual correlation among OCT biomarkers and their relationship with visual and anatomic outcomes both at baseline and over the follow-up period.
The mean follow-up was 71.2 months (SD 28.4; minimum 12-maximum 111). Here are some of the findings:
• At baseline, the prevalence of SRD+ was 27.8 percent, and a high number of HRF were detected in 41.4 percent of eyes.
• A significant reduction in the number of HRF, CMT, CRT and in the prevalence of SND was recorded in the post-loading phase (p<0.0001).
• In DME recurrences, presence of SND+ and HRF+ was significantly more frequent in eyes with baseline SND+ and HRF+ compared to eyes presenting baseline SND- and HRF- (p<0.0001).
• No role of SND (p=0.926) and HRF (p=0.281) as baseline predictors of visual and anatomic outcomes was demonstrated, while a worse visual outcome was significantly correlated with a higher incidence of relapsing SND+ (p<0.0001) and HRF+ (p<0.0028) throughout the follow-up period.
In this study, SND and HRF were frequently present in DME recurrences with the same pattern exhibited at baseline, suggesting that these OCT biomarkers may characterize a specific pattern of DME that repeats over time. Moreover, the results suggested that the persistence and recurrence of SND and HRF may account for a decrease in visual function more than the baseline prevalence of these biomarkers. Further studies are required to confirm these findings
Source: Maggio E, Mete M, Sartore M, et al. Temporal variation of optical coherence tomography biomarkers as predictors of anti-VEGF treatment outcomes in diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2021; Oct 18. [Epub ahead of print].
Visual Outcomes & Morphologic Biomarkers of Vision Loss in DME Eyes Treated with Anti-VEGF Therapy
Investigators analyzed the morphological characteristics and long-term visual outcomes in eyes with diabetic retinopathy and diabetic macular edema treated with anti-vascular endothelial growth factor therapy, as part of a retrospective clinical cohort study.
They included subjects with a long-term follow-up and evidence of resolved DME in at least one visit (study visit) after five years of follow-up following the initiation of anti-VEGF therapy. At the study visit, structural OCT scans were reviewed for qualitative features reflecting a distress of the neuroretina or retinal pigment epithelium. A quantitative topographical assessment of the inner and outer retinal thicknesses was also provided.
Sixty-one eyes (50 patients) were included and divided into two subgroups according to the visual acuity at the study visit, yielding a group of 24 eyes with a VA <20/40 ("poor/intermediate vision" group), and 37 eyes with a VA ≥20/40 ("good vision" group). Here are some of the findings:
• The external limiting membrane (ELM) and RPE bands were more frequently disrupted/absent in the poor/intermediate vision group (p=0.003 and p=0.019).
• Disorganization of retinal inner layers was more prevalent in the "poor/intermediate vision" group (p=0.013).
• Foveal and parafoveal outer retinal thicknesses were reduced in poor/intermediate vision eyes (p=0.022 and p=0.044).
• Multivariate stepwise linear regression analysis demonstrated that VA was associated with appearance of the RPE and ELM (p<0.0001 and p=0.048, respectively), and foveal and parafoveal outer retinal thicknesses (p=0.046 and p=0.035, respectively).
Investigators found that modifications in the outer retina and RPE represented OCT biomarkers of long-term visual outcomes in eyes with DME treated with anti-VEGF.
SOURCE: Borrelli E, Grosso D, Barresi C, et al. Long-term visual outcomes and morphologic biomarkers of vision loss in eyes with diabetic macular edema treated with anti-VEGF therapy. Am J Ophthalmol 2021; Sep 9. [Epub ahead of print].
Cost Effectiveness Analysis of Intravitreal Aflibercept for Preventing Progressive DR
Researchers calculated costs required to prevent center-involved diabetic macular edema (CI-DME) or proliferative diabetic retinopathy (PDR), and to improve the diabetic retinopathy severity score (DRSS) with intravitreal anti-VEGF injections, as reported for aflibercept in two randomized control trials.
They used a cost-effectiveness analysis modeling based on published data. They analyzed results from PANORAMA and the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol W. Parameters collected included DRSS score, risk reduction of PDR, risk reduction of CI-DME and number of treatments required. Costs were modeled based on 2020 Medicare reimbursement data practice settings of hospital-based facilities and non-facilities.
Main outcome measure included cost to prevent cases of PDR and CI-DME, and to improve DRSS stage.
Here are some of the findings:
• Over two years in Protocol W, the cost required to prevent one case of PDR was $83,000 ($72,400) in the facility (non-facility) setting; in PANORAMA, the corresponding two-year costs were $89,400 ($75,000) for the 2Q16 arm and $91,200 ($89,900) for the 2Q8PRN arm.
• To prevent one case of CI-DME with vision loss in Protocol W, the cost was $154,000 ($133,000).
• For all CI-DME, with and without vision loss, in PANORAMA, the costs to prevent a case were $70,900 ($59,500) for the 2Q16 arm and $90,000 ($88,800) for the 2Q8PRN arm.
• In Protocol W, the overall accumulated total for cost/DRSS unit change at the two-year point for facility (non-facility) setting was $2,700 ($2,400)/DRSS. In the first year, the cost was $2,100 ($1,800)/DRSS, and in the second year it was $6,100 ($5,300)/DRSS.
Researchers found a considerable cost associated with the prevention of PDR and CI-DME with intravitreal aflibercept injections. They added that a price per unit of change in diabetic retinopathy severity score is a new parameter that might serve as a benchmark in future utility analyses that could be used to bring perspective to cost-utility considerations.
SOURCE: Patel NA, Yannuzzi NA, Lin J, et al. A cost effectiveness analysis of intravitreal aflibercept for the prevention of progressive diabetic retinopathy. Ophthalmol Retina 2021; Sep 18. [Epub ahead of print].
Refillable Anti-VEGF Port Delivery System Approved
In October, the FDA approved Genentech’s port-delivery system with ranibizumab, now called Susvimo (ranibizumab injection) 100 mg/mL, for intravitreal use via ocular implant for the treatment of neovascular age-related macular degeneration that’s previously responded to at least two anti-vascular endothelial growth factor (VEGF) injections.
Genentech says that Susvimo is the only FDA-approved treatment for wet AMD that offers as few as two treatments per year. Susvimo is a refillable, permanent eye implant that continuously releases a customized formulation of ranibizumab to the eye. The implant is surgically inserted into the eye during a one-time, outpatient procedure and refilled every six months.
The approval is based on the results of the Phase III Archway study, which the company says showed wet AMD patients treated with Susvimo achieved vision gains equivalent to monthly ranibizumab injections through 40 weeks of treatment.
Xipere is Here
Also in October, the FDA approved Xipere, (triamcinolone acetonide injectable suspension) Bausch + Lomb/Clearside Biomedical’s suprachoroidal injection for the treatment of uveitic macular edema. Xipere is the first drug to use the suprachoroidal space, which the company says provides targeted delivery and compartmentalization of medication. To deliver the drug to the suprachoroidal space, the physician uses the proprietary SCS Microinjector, which was developed by Clearside.
The FDA approval of Xipere was based on results from PEACHTREE, a randomized, multicenter, double-masked, sham-controlled Phase III clinical trial of 160 patients with macular edema associated with uveitis. The primary efficacy endpoint was improvement in best-corrected vision by at least 15 letters from baseline after 24 weeks. The drug’s maker says that, in the trial, a statistically significantly greater proportion of patients treated with Xipere (47 percent) achieved at least a 15-letter improvement in BCVA than patients in the control arm (16 percent, p<0.01) at Week 24.
The company says the drug will be available for sale in the first quarter of 2022. Read more.
Novartis Files Applications for New Beovu Indication
Novartis recently announced that the US Food and Drug Administration has accepted the company’s supplemental Biologics License Application (sBLA) and that the European Medicines Agency (EMA) has validated the type-II variation application for Beovu (brolucizumab) 6 mg for the treatment of diabetic macular edema. Additionally, the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) accepted an application for Beovu for use in the treatment of DME. Regulatory decisions for Beovu in DME are expected in mid-2022 for the U.S. and Europe. Read more.
SOURCE: Novartis, October 2021
iCare Announces FDA Approval of Eidon Ultra-widefield Lens Module
The Eidon Ultra-Widefield Lens module from iCare received FDA 510(k) approval for distribution in the United States. The ultra-widefield module enables the capture of 120-degree images of the retina in a single shot or up to 200 degrees with its expanded Mosaic function. The company says its image quality enables the detection of small details and signs of pathologies from the center to the periphery. The ultra-widefield lens module can be retrofitted to most Eidon fundus imaging systems. Read more.
SOURCE: iCare October 2021
Outlook Therapeutics Reports New Safety Data from Phase III NORSE TWO Trial, Presents Data at ASRS
Outlook Therapeutics announced new 12-month safety data from the Phase III NORSE TWO trial of ONS-5010 / Lytenava (bevacizumab-vikg) for treatment of neovascular age-related macular degeneration. The company says that the topline data previously reported showed a robust safety profile. Read more.
In addition, the company presented results from its NORSE THREE supplemental safety study evaluating ONS-5010 / Lytenava (bevacizumab-vikg) at the 39th Annual Meeting of the American Society of Retina Specialists in San Antonio (October 8 to 12). The company says that data from NORSE THREE indicated that ONS-5010 showed no intraocular inflammation or vasculitis, and the frequency and incidence of adverse events and ocular adverse events were low. The most common adverse event in the study eye was conjunctival hemorrhage related to the injection procedure.
SOURCE: Outlook Therapeutics, September, October 2021
Adverum Presents OPTIC Data
Adverum Biotechnologies presented long-term data from the OPTIC clinical trial of ADVM-022 single, in-office intravitreal injection gene therapy in patients requiring frequent anti-VEGF injections for neovascular age-related macular degeneration. Safety and efficacy data from patients followed through two years post-injection, presented at the Retina Society’s annual scientific meeting included: >80 percent reduction in annualized anti-VEGF injection frequency in patients who previously required frequent injections; >50 percent of patients (8/152) after median follow-up of 1.7 years remained entirely free of any supplemental anti-VEGF injection; and robust aflibercept expression levels continued to be sustained through two years after a single injection of ADVM-022, the company says. Read more.
SOURCE: Adverum Biotechnologies, October 2021
Regenxbio Reports Initial Data from Phase II AAVIATE Trial of RGX-314, Presents Data at ASRS
Regenxbio announced initial data from the ongoing Phase II AAVIATE trial of its gene therapy RGX-314 for the treatment of wet age-related macular degeneration using in-office suprachoroidal delivery, presented at the Retina Society 54th Annual Scientific Meeting. AAVIATE is a multicenter, open-label, randomized, active-controlled, dose-escalation trial that will evaluate the efficacy, safety and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector. Read more.
In addition, the company announced initial data from the ongoing Phase II ALTITUDE trial of RGX-314 for the treatment of diabetic retinopathy without center-involved diabetic macular edema using in-office suprachoroidal delivery. As of September 29, the company says RGX-314 was reported to be well-tolerated in the 15 patients dosed with RGX-314 in cohort 1.
SOURCE: Regenxbio, both October 2021
EyePoint Presents Preliminary Safety Data from Phase I DAVIO Trial and Yutiq CALM Registry Study
EyePoint Pharmaceuticals announced interim safety data from its Phase I clinical trial of EYP-1901, a potential twice-yearly sustained delivery anti-VEGF treatment targeting wet age-related macular degeneration. The company says that preliminary three-month safety data for all patients from its ongoing DAVIO trial of EYP-1901 continues to demonstrate an excellent safety profile with no serious ocular or systemic adverse events reported to date. The company also recently shared preliminary results from Yutiq CALM, a real-world registry study of the fluocinolone acetonide intravitreal implant 0.18 mg in chronic noninfectious posterior uveitis. Read more.
Source: EyePoint Pharmaceuticals, October 2021
4D Molecular Files IND Application for 4D-150
4D Molecular Therapeutics announced the FDA accepted the Investigational New Drug Application for 4D-150 for wet age-related macular degeneration, enabling the initiation of 4D-150 Phase I/II clinical trials. 4D-150 is a dual-transgene, intravitreal gene therapy. Read more.
SOURCE: 4D Molecular Therapeutics, October 2021
Gyroscope Announces Interim Phase I/II Data on Gene Therapy for GA
Positive interim data from the ongoing open-label Phase I/II FOCUS clinical trial of Gyroscope Therapeutics’ investigational, one-time gene therapy, GT005, for geographic atrophy secondary to age-related macular degeneration were presented at the Retina Society’s annual scientific meeting. Safety data from 28 patients showed GT005 continued to be well- tolerated with no treatment-related serious adverse events, the company says. Read more.
SOURCE: Gyroscope Therapeutics, September 2021
Lineage Announces Data on OpRegen in Geographic Atrophy
Lineage Cell Therapeutics reported updated findings from its ongoing, 24-patient Phase I/IIa clinical study of lead candidate OpRegen. OpRegen is an investigational cell therapy consisting of allogeneic retinal pigment epithelium cells, administered in a single surgery to the subretinal space for the treatment of dry age-related macular degeneration with geographic atrophy. Lineage says that, overall, OpRegen was well-tolerated with no new unexpected ocular or systemic adverse events, or serious adverse events not previously reported. Read more.
SOURCE: Lineage Cell Therapeutics, September 2021
PALADIN Reveals Iluvien’s Ability to Reduce Treatment Burden in DME
Alimera Sciences says data presented at the American Society of Retina Specialists demonstrated significant reductions in treatment burden in patients receiving Iluvien for diabetic macular edema. The real-world data from the Phase IV PALADIN study showed that patients receiving one or less total anti-VEGF injections per year for their DME after the Iluvien injection increased threefold from prior to the Iluvien injection. The data also showed that the percent of patients who needed more than four anti-VEGF DME treatments per year was reduced by half. Read more.
SOURCE: Alimera Sciences, October 2021
GenSight Announces FDA Grants Fast Track Designation to RP Treatment
GenSight Biologics announced that the FDA granted Fast Track Designation to GS030, which combines AAV2-based gene therapy with optogenetics to treat retinitis pigmentosa. PIONEER, a Phase I/II, multicenter, open-label, dose-escalation clinical trial to evaluate the safety and tolerability of GS030 in subjects with late-stage RP, is being conducted in three centers in the United States, United Kingdom and France. Read more.
SOURCE: GenSight Biologics, October 2021
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