From the editors of Review of Ophthalmology and Retina Specialist
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.
Phase III Randomized Controlled Study of Abicipar in nAMD: Two-Year Results
Investigators compared the efficacy and safety of abicipar every eight weeks and quarterly (after initial doses) vs. ranibizumab every four weeks in treatment-naïve patients with neovascular age-related macular degeneration.
Two randomized, multicenter, double-masked, parallel-group, active-controlled Phase III clinical trials (CEDAR, SEQUOIA) with identical protocols were conducted. Data from both trials were pooled for analysis.
Patients with active choroidal neovascularization secondary to AMD and best-corrected visual acuity of 24-73 Early Treatment Diabetic Retinopathy Study letters in the study eye were enrolled.
Patients (n=1,888) were randomized in a 1:1:1 ratio to treatment with abicipar of:
- abicipar 2 mg every eight weeks after three initial doses at baseline, and at weeks four and eight (Q8);
- abicipar 2 mg every 12 weeks after three initial doses at baseline and at weeks four and 12 (Q12); or
- ranibizumab 0.5 mg every four weeks (Q4).
The primary efficacy endpoint was proportion of patients with stable vision (defined as <15-letter loss in BCVA from baseline) in the study eye at week 52. Secondary endpoints included change from baseline in BCVA and central retinal thickness at week 52. Safety measures included adverse events.
Here are some of the findings:
- The proportion of patients with stable vision at week 52 was:
- 93.2 percent in the abicipar Q8 group;
- 91.3 percent in the abicipar Q12 group; and
- 95.8 percent in the ranibizumab Q4 group.
- Both abicipar Q8 and Q12 were noninferior to ranibizumab Q4.
- Week 52 mean change from baseline was:
- in BCVA
- 7.5 letters in the abicipar Q8 group;
- 6.4 letters in the abicipar Q12 group; and
- 8.4 letters in the ranibizumab Q4 groups; and
- in CRT
- -144 μm in the abicipar Q8 group;
- -145 μm in the abicipar Q12 group; and
- -144 μm in the ranibizumab Q4 group.
- Incidence of intraocular inflammation (IOI) AEs was:
- 15.4 percent in the abicipar Q8 group;
- 15.3 percent in the abicipar Q12 group; and
- 0.3 percent in the ranibizumab Q4 group.
- The IOI AEs were typically mild or moderate in severity and treated with topical corticosteroids; 62 of 192 patients (32.3 percent) received oral and/or injectable corticosteroids.
Investigators wrote that abicipar Q8 and Q12 were noninferior to ranibizumab Q4 in the primary endpoint of stable vision at week 52. They added that IOI was more frequent with abicipar, although quarterly and Q8 abicipar reduced nAMD disease and treatment burden compared with monthly treatment.
SOURCE: Kunimoto D, Yoon YH, Wykoff CC, et al; CEDAR and SEQUOIA Study Groups. Efficacy and safety of abicipar in neovascular age-related macular degeneration: 52-week results of Phase 3 randomized controlled study. Ophthalmology 2020 Oct;127(10):1331-44.
Ladder Phase II Trial of the Port Delivery System with Ranibizumab for nAMD
Scientists reported the Phase II results from the Ladder clinical trial of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration, as part of a multicenter, randomized, active treatment-controlled trial.
Participants included individuals diagnosed with nAMD with a documented response to anti-vascular endothelial growth factor treatment who received study treatment (n=220).
They were randomized 3:3:3:2 to treatment with the PDS filled with ranibizumab 10 mg/mL, 40 mg/mL, and 100 mg/mL formulations or monthly intravitreal ranibizumab 0.5 mg injections.
Main outcome measures included end of study results for the time to first meeting refill criteria (first refill), mean change from baseline for best-corrected visual acuity and central foveal thickness (CFT), and safety.
Here were some of the findings:
- At study end, the mean time on study was 22.1 (range: 10.8 to 37.6) months for all PDS patients.
- Median time to first refill was 8.7, 13 and 15.8 months; and 28.9 percent, 56 percent and 59.4 percent of patients went 12 months or longer without meeting refill criteria in the PDS 10 mg/mL, 40 mg/mL, and 100 mg/mL treatment arms, respectively.
- At month 22, the observed mean BCVA change from baseline was ‒4.6, ‒2.3, +2.9, and +2.7 Early Treatment Diabetic Retinopathy Study letters in the PDS 10 mg/mL, 40 mg/mL, 100 mg/mL and monthly intravitreal ranibizumab 0.5 mg treatment arms, respectively.
- At month 22, the observed mean CFT change from baseline was similar in the PDS 100 mg/mL and monthly intravitreal ranibizumab 0.5 mg treatment arms. No new safety signals were detected during the additional follow-up.
Over a mean of 22 months’ follow-up, vision and anatomic outcomes were comparable between the PDS 100 mg/mL and monthly intravitreal ranibizumab 0.5 mg arms, with a lower total number of ranibizumab treatments with the PDS. The Ladder end of the study findings were consistent with the primary analysis, and the PDS was generally well-tolerated throughout the study period. The PDS has the potential to reduce treatment burden in patients with nAMD while maintaining vision, researchers say.
SOURCE: Khanani AM, Callanan D, Dreyer R, MD, et al. End of study results for the ladder phase 2 trial of the port delivery system with ranibizumab for neovascular age-related macular degeneration. Ophthalmology Retina 2020; Nov. 17. [Epub ahead of print].
Insights From Survival Analyses Over 12 Years of Anti-VEGF for nAMD
The authors of this study say that although multiple imputation models for missing data and the use of mixed-effects models generally provide better outcome estimates than using observed data or last observation in clinical trials, such approaches usually can’t be applied to visual outcomes from retrospective analyses of clinical practice settings (i.e., real-world outcomes). In the study, the researchers explored the potential usefulness of survival analysis techniques for retrospective clinical practice visual outcomes.
This retrospective cohort study covered a 12-year observation period at a tertiary eye center. Of 10,744 eyes with neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor therapy between October 28, 2008, and February 1, 2020, 7,802 eyes met study criteria (treatment-naive, first-treated eyes starting anti-VEGF therapy). Eyes were excluded from the analysis if they received photodynamic therapy or macular laser, any previous anti-VEGF therapy, treatment with anti-VEGF agents other than ranibizumab or aflibercept, or had an unknown visual acuity value at first injection.
Kaplan-Meier estimates and Cox proportional hazards modeling were used to consider VA reaching an Early Treatment Diabetic Retinopathy Study letter score of 70 (Snellen equivalent, 20/40) or better, duration of VA sustained at or better than 70, and VA declining to 35 (20/200) or worse.
A total of 7,802 patients (mean age, 78.7 ±8.8 years; 4,776 women [61.2 percent]) were included in the study. Here were some of the findings:
- The median time to attaining a VA letter score greater than or equal to 70 was 2 years (CI, 1.87 to 2.32) after the first anti-VEGF injection.
- Predictive features were:
- baseline VA (hazard ratio [HR], 1.43 per five ETDRS letter score or one line; CI, 1.40 to 1.46);
- baseline age (HR, 0.88 per five years; CI, 0.86 to 0.90); and
- injection number (HR, 1.12; CI, 1.10 to 1.15).
- Of the 4,439 of 7,802 patients (57 percent) attaining this outcome, median time sustained at an ETDRS letter score of 70 or better was 1.1 years (CI, 1.1 to 1.2).
Researchers wrote that patients with nAMD beginning anti-VEGF therapy were more likely to experience positive visual outcomes within the first two years after treatment, typically maintaining this outcome for 1.1 years but then deteriorating to poor vision within 8.7 years. They added that this data set, combined with the statistical approach for retrospective analyses, may provide long-term prognostic information for patients newly diagnosed with this condition.
SOURCE: Dun JF, Keenan TD, Faes L, et al. Insights from survival analyses during 12 years of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration. JAMA Ophthalmol 2020; Nov 19. [Epub ahead of print].
Stages of Drusen-associated Atrophy in AMD Visible Via Histologically Validated Fundus Autofluorescence
Researchers sought to determine histologic correlates for defined stages of drusen-associated atrophy observed with multimodal imaging including fundus autofluorescence (FAF) and color fundus photography (CFP) in eyes with advanced age-related macular degeneration, as part of a case study and clinicopathologic correlation.
A white woman in whom AMD findings of inactive subretinal fibrosis (right eye) and untreated non-exudative type 1 macular neovascularization (left eye) was followed for nine years before death at age 90 years.
The eyes were preserved 6.25 hours after death and were post-fixed in osmium tannic acid paraphenylenediamine and prepared for sub-micrometer epoxy resin sections (n=115 and 90 in right and left eyes, respectively, with 19 aligned to clinical OCT B-scans. Drusen visible by CFP at the last visit were assigned to four stages of in vivo FAF: stage 1, isoFAF, no obvious FAF alteration; stage 2, mildly uniform hyperFAF; stage 3, a ring of hyperFAF around a center of hypoFAF; and stage 4, uniform hypoFAF.
Main outcome measures included light microscopic morphology at known FAF stages, including druse size, druse contents and changes in overlying retinal pigment epithelium, photoreceptors and external limiting membrane.
Here were some of the findings:
- Histology of 166 drusen demonstrated that stage 1 iso-FAF drusen were visible in CFP.
- HyperFAF in stage 2 corresponded to short photoreceptors and complete coverage by RPE.
- HypoFAF in stage 3 and 4 corresponded to different extents of RPE atrophy (RPE gap and no RPE, respectively).
- Of stage 4 drusen, 67 percent have no ONL and an undetectable ELM.
- Stage 4 includes a high proportion of refractile drusen (82 percent) with many calcific nodules, visible in CFP.
Researchers wrote that the data supported four FAF stages of drusen-associated atrophy. They reported that: Stage 2 was the earliest detected stage in which loss of screening by photoreceptor photopigment contributed to uniform hyperFAF; stages 3 and 4 were consistent with incomplete RPE and outer retinal atrophy (iRORA) as defined by the Classification of Atrophy Meetings group. Furthermore, researchers wrote, loss of RPE, ONL and ELM in stage 4 indicated that atrophy can begin over individual drusen. Researchers wrote that their findings will help the identification of new therapeutic approaches and clinical study endpoints.
SOURCE: Chen L, Messinger JD, Ferrara D, et al. Stages of drusen-associated atrophy in age-related macular degeneration visible via histologically validated fundus autofluorescence. Ophthalmology Retina 2020; Nov 17. [Epub ahead of print].
Impact of Scotopic Microperimetric Sensitivity & Inner Choroid Flow Deficits on GA Progression
Researchers assessed the role of microperimetric retinal sensitivity and inner choroid flow deficits in predicting the development of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) in intermediate AMD.
Thirty eyes with intermediate AMD evaluated at the Doheny-UCLA Eye Centers were enrolled in this prospective IRB-approved study. Subjects underwent several diagnostic tests:
• 6 × 6-mm swept-source optical coherence tomography angiography with the IC slab used to quantify flow deficits;
• 20 × 20-degree spectral-domain OCT to monitor progression to iRORA; and
• scotopic microperimetric retinal sensitivity within an area of 18 degrees centered on the fovea. All subjects were followed-up for 24 months. The baseline inner choroid flow deficits and microperimetric retinal sensitivity were correlated with the development of iRORA. At 24-month follow-up, the AMD stage was re-assessed, and eyes were divided into two subgroups based on iRORA development.
Twenty-eight eyes completed the two-year follow-up. At baseline, the mean microperimetric retinal sensitivity was 13.40 ±4.66 dB and the mean inner choroid flow deficit was 27.55 ±8.67 percent. The morpho-functional regression showed a significant correlation between baseline microperimetric retinal sensitivity and inner choroid flow deficits, and iRORA development within 24 months (R2=0.744; p<0.05). A Kaplan-Meier survival curve was fit to determine the cumulative incidence of iRORA over the 24 months..
Researchers reported that a lower microperimetric retinal sensitivity and greater inner choroid flow deficits at baseline were predictors of progression to iRORA in intermediate AMD eyes. They added that these parameters may be useful biomarkers for risk stratification and prognostication.
SOURCE: Corradetti G, Tiosano L, Nassisi M, et al. Scotopic microperimetric sensitivity and inner choroid flow deficits as predictors of progression to nascent geographic atrophy. Br J Ophthalmol 2020; Nov 10. [Epub ahead of print].
Relationship of Topographic Distribution of GA to VA in Nonexudative AMD
Scientists analyzed the topographic distribution of geographic atrophy and identified a continuous anatomic endpoint that correlates with visual acuity in eyes with GA, as part of a retrospective analysis of a multicenter, prospective, randomized controlled trial.
The study included Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration.
Scientists manually delineated GA on 1,654 fundus photographs of 365 eyes. They measured GA areas in nine macular subfields in the Early Treatment for Diabetic Retinopathy Study grid, and correlated them with VA via a mixed-effects model. They determined the optimal diameter for the central zone by varying the diameter from zero to 10 mm until the highest r2 between GA area in the central zone and VA was achieved. The scientists estimated the VA decline rate over eight years using a linear mixed model. Main outcome measures included GA area in macular subfields and VA.
Here were some of the findings.
- The percentage of area affected by GA declined as a function of retinal eccentricity.
- GA area was higher in the temporal than nasal region (1.30 ±1.75 vs. 1.10 ±1.62 mm2; p=0.005), and in the superior than inferior region (1.26 ±1.73 vs. 1.03 ±1.53 mm2; p<0.001).
- Total GA area correlated poorly with VA (r2=0.07).
- Among GA areas in nine subfields, only GA area in the central zone was independently associated with VA (p<0.001).
- Scientists determined 1 mm as the optimal diameter for the central zone, in which GA area correlated best with VA (r2=0.45).
- On average, full GA coverage of the central 1-mm-diameter zone corresponded to 34.8 ETDRS letters decline in VA.
- The VA decline rate was comparable between eyes with initial noncentral and central GA before GA covered the entire central 1-mm-diameter zone (2.7 vs. 2.8 ETDRS letters/year; p=0.94).
Scientists wrote that the prevalence of GA varies significantly across different macular regions. They added that, although total GA area was poorly associated with VA, GA area in the central 1-mm-diameter zone was significantly correlated with VA and may serve as a surrogate endpoint in clinical trials.
SOURCE: Shen LL, Sun M, Ahluwalia A, et al. Relationship of topographic distribution of geographic atrophy to visual acuity in nonexudative age-related macular degeneration. Ophthalmology Retina 2020; Nov 16. [Epub ahead of print].
New Model of Care for DR Complications: The EMERALD Study
Researchers wrote that increasing diabetes prevalence and the advent of new treatments for diabetes’ major visual-threatening complications (diabetic macular edema and proliferative diabetic retinopathy) requiring frequent and lifelong follow-up have markedly increased hospital demands. Given that resulting delays in the evaluation/treatment of patients can lead to sight loss, they added that strategies to increase the capacity of medical retina clinics are urgently needed. EMERALD tested the diagnostic accuracy, acceptability and cost of a new diagnostic pathway for people with previously treated DME/PDR. Optos provided instruments for the researchers.
The prospective, multicenter cross-sectional study involving 13 hospitals in the United Kingdom included adults with type 1 or 2 diabetes who successfully treated DME/PDR, and who had active or inactive disease at the time of enrollment.
Researchers evaluated a new diagnostic pathway involving multimodal imaging (spectral-domain optical coherence tomography for DME, and 7-field Early Treatment Diabetic Retinopathy Study and ultra-widefield fundus images for PDR) interpreted by trained non-medical staff to detect reactivation of disease. The researchers compared the new pathway with the current standard of care (ophthalmologists’ face-to-face examinations).
The primary outcome was sensitivity of the new pathway. The secondary outcomes were:
• agreement between pathways;
• percentage of patients requiring subsequent ophthalmologist assessment unable to undergo imaging or with inadequate images/indeterminate findings.
Here were some of the findings:
• The new pathway had sensitivity of 97 percent (CI, 92 to 99 percent) and specificity of 31 percent (CI, 23 to 40 percent) to detect DME.
• For PDR, 7-field ETDRS, sensitivity (85 percent, 95 percent CI, 77 to 91 percent) and specificity (48 percent; CI, 41 to 56 percent) were comparable to UWF sensitivity (83 percent, CI, 75 to 89 percent) and specificity (54 percent; CI, 46 to 61 percent).
• For detection of high-risk PDR, sensitivity (87 percent, CI, 78 to 93 percent) and specificity (49 percent, CI, 42 to 56 percent) were higher when using UWF images vs. sensitivity (80 percent, CI, 69 to 88 percent) and specificity (40 percent, CI, 34 to 47 percent) for 7-field ETDRS.
• Participants preferred ophthalmologist assessments; when ophthalmologists were absent, they requested immediate feedback from graders and maintained periodic ophthalmologist evaluations.
• Researchers suggested the new pathway, compared with the current standard of care, could save $1,792.61/100 DME visits, and between $594.53 and $1,533.39/100 PDR visits. Researchers reported that fully-automated localization and quantification of IRF/SRF over time shed light on the fluid dynamics in each disease. They found a specific anatomical response by IRF/SRF to anti-VEGF therapy in all diseases studied.
Researchers reported that the new ophthalmic grader pathway had acceptable sensitivity, and may free up resources for ophthalmologists by helping to evaluate patients with DME and PDR. They say the study’s limitations included the fact that images of the iris and anterior chamber angle weren’t obtained for the evaluation of people with PDR, so any new vessels that developed—though rare—would be missed. Additionally, fluorescein angiography wasn’t performed to determine the actual activity of the PDR.
SOURCE: Lois N, Cook JA, Wang A, et al; EMERALD Study Group. Evaluation of a new model of care for people with complications of diabetic retinopathy: The EMERALD Study. Ophthalmology 2020; Oct 29. [Epub ahead of print].
Effect of Suspended Scattering Particles & OCTA Vessel Density on DME
Scientists studied the effect of suspended scattering particles in motion (SSPiM) on optical coherence tomography angiography vessel density metrics in eyes with diabetic macular edema.
Thirty-four eyes with DME from 27 patients (16 males and 11 females, 61.4 ±9.6 years) with DME were included in this retrospective cohort study. Among these eyes, 19 (55.9 percent) showed the SSPiM artifact on OCTA. All participants underwent 3- and 6-mm OCTA. Perfusion density and skeletonized vessel density were calculated for the superficial capillary plexus (SCP) and deep capillary plexus (DCP), and compared between eyes with and without SSPiM. Additionally, foveal vessel density in a 300-µm-wide region around the foveal avascular zone (FAZ) was evaluated on 3-mm OCTA scans. The main outcome measures were vessel density in the SCP and the DCP.
Here were some of the findings:
• Among the 3-mm OCTA images, no statistically significant difference was found in SCP vessel density in eyes with and without SSPiM (p=0.98).
• Vessel density in the DCP (p=0.001 and p=0.028 for perfusion and skeletonized vessel density, respectively) and FAZ (p=0.03) on 3-mm OCTA scans was significantly higher in DME eyes with SSPiM.
• No statistically significant differences were found in SCP and DCP vessel density between eyes with and without SSPiM, based on 6-mm OCTA scans.
Scientists determined that the presence of suspended scattering particles in motion led to an overestimation of DCP vessel density in eyes with DME when 3-mm OCTA scans were used for analysis.
SOURCE: Maltsev DS, Kulikov AN, Kazak AA, et al. Suspended scattering particles in motion may influence optical coherence tomography angiography vessel density metrics in eyes with diabetic macular edema. Retina 2020; Oct 30. [Epub ahead of print].
Outcomes in Retinal Vein Occlusions Presenting with Poor Visual Acuity Treated with Anti-VEGF Therapy: Prognosis and Predictive Factors
Researchers presented visual acuity and optical coherence tomography outcomes in patients with retinal vein occlusions treated with anti-vascular endothelial growth factor agents presenting with poor initial visual acuity. They aimed to identify relevant factors that may portend differential outcomes in this important patient population.
The retrospective chart review included 52 patients with recent RVO, treated with anti-VEGF therapy, presenting with habitual corrected visual acuity (HCVA) of <20/320 prior to any ocular therapy, with at least six months of follow-up.
Visual acuity, spectral-domain OCT, injection details, and the development of neovascular sequelae or need for adjunct therapies were recorded for consecutive visits after meeting vision criteria (max 16 visits). In the central retinal vein occlusion cohort, univariate and multivariate analyses were performed to identify factors predictive of outcomes, and the incidence of sequelae was studied with survival analysis.
Main outcome measures included the change in approximate ETDRS letter score at six and 12 months. Here were some of the findings:
- CRVO patients (n=39) gained a median of +20 letters relative to baseline at six and 12 months, and showed a change in CST of -504.1 µm at six months and -553.2 µm at 12 months.
- Branch retinal and hemiretinal vein occlusion patients (n=13) gained a median of +45 letters at six months and +57.5 letters at 12 months, and showed reductions of 299.6 µm of CST on SD-OCT at six months and 355.2 µm of CST on SD-OCT and 12 months.
- For CRVO patients, greater time from symptom onset to first injection was predictive of less optimistic letter gains at six and 12 months in both unadjusted and adjusted models (p<0.0001 for all measures).
- A delay from symptom onset to first injection of ≥30 days predicted higher incidence of both neovascular (HR 11.036; CI, 1.807 to 67.393) and total (HR 11.425; CI, 1.940 to 67.300) events.
Researchers wrote that patients with RVO presenting with poor initial visual acuity showed visual and anatomic benefit with anti-VEGF therapy, most often observed shortly after initiation of treatment. They added that, in CRVOs, even minor delays between symptom onset and first injection led to less optimistic vision gains and were associated with higher incidence of negative sequelae.
Source: Light JG, Tian J, Wenick A. Outcomes in retinal vein occlusions presenting with poor visual acuity treated with anti-VEGF therapy: Prognosis and predictive factors. Ophthalmol Retina 2020; Nov 20. [Epub ahead of print].
En face Image-based Analysis of Epiretinal Membrane Formation After Surgery for Idiopathic Epiretinal Membrane
Investigators analyzed en face epiretinal membrane images constructed using swept-source optical coherence tomography and determined the incidence of ERM formation after ERM surgery and the effects of ERM formation on visual functions, as part of a retrospective, consecutive observational study.
Participants included a consecutive series of 73 eyes (71 patients) with idiopathic ERM that underwent vitrectomy with both ERM and internal limiting membrane (ILM) peelings.
Investigators retrospectively reviewed the data of the 73 eyes included in the study. During the surgery, ERM was removed as extensively as possible, and ILM was removed such that the area of ILM peeling was at least larger than the parafoveal area. All patients underwent comprehensive ophthalmological exams, including assessments of the best-corrected visual acuity and metamorphopsia, before and at two weeks and six months after the surgery. En face images constructed using SS-OCT were used to investigate ERM formation.
Main outcome measures included the incidence of ERM formation at six months after the surgery, effects of ERM formation on visual function, and relationship between ERM formation and the extents of ERM and ILM peelings.
Here were some of the findings:
- At six months after ERM and ILM peeling, eight eyes (11 percent) showed ERM formation (formation group).
- Twenty eyes (27.4 percent) exhibited remnant ERM without ERM formation (remnant group), while 45 eyes (61.6 percent) showed no ERM [ERM(-) group].
- In both the remnant and ERM(-) groups, BCVA and metamorphopsia showed significant improvements after ERM surgery (both p<0.01); these improvements weren’t seen in the formation group (p=0.067 and 0.053, respectively).
- However, no significant differences were found in pre- and postoperative BCVAs and metamorphopsia among the three groups.
- In the formation group, ERM formation occurred only in the area with residual ILM.
- The majority of the patients who underwent ILM peelings where the area of the peeling covered the ERM belonged to the ERM(-) group (97.7 percent, p<0.01).
Investigators wrote that ERM formation didn’t significantly affect visual function when the area of ILM peeling was larger than the parafoveal area. They added that, when the ILM peeling area covered the ERM area, postoperative ERM formation could be prevented.
SOURCE: Kanzaki S, Kanzaki Y, Doi S, et al. En face image-based analysis of epiretinal membrane formation after surgery for idiopathic epiretinal membrane. Ophthalmol Retina 2020; Oct 28. [Epub ahead of print].
NOVARTIS REPORTS DATA & POST-HOC ANALYSIS OF BEOVU TRIALS
Novartis reported initial findings from a coalition convened to answer key questions related to treatment with Beovu (brolucizumab) for adults with wet age-related macular degeneration. Analyses of U.S. real-world and Phase III data presented at the American Academy of Ophthalmology virtual meeting identified baseline patient characteristics potentially associated with the incidence of inflammation-related adverse events that may occur following treatment with Beovu. Novartis says it has a comprehensive program under way to examine the root cause and potential risk factors for these events, and to identify mitigation strategies and treatment protocols. Read more.
SOURCE: Novartis, November 2020
KODIAK COMPLETES ENROLLMENT OF DAZZLE PHASE IIB/III KSI-301 STUDY
Kodiak Sciences announced that recruitment concluded in its DAZZLE pivotal study of KSI-301, an anti-VEGF antibody biopolymer conjugate, in patients with neovascular age-related macular degeneration. Read more.
SOURCE: Kodiak, November 2020
ADVERUM ANNOUNCES INTERIM DATA FROM OPTIC PHASE I TRIAL
Adverum Biotechnologies announced positive new interim data from cohorts one to four in the OPTIC Phase I clinical trial of ADVM-022 intravitreal injection gene therapy in individuals requiring frequent anti-VEGF injections for wet AMD. Adverum says the therapy continues to maintain efficacy at high and low doses. Read more.
SOURCE: Adverum Biotechnologies, October 2020
INNOVENT ANNOUNCES PHASE I IBI302 TRIAL RESULTS
Innovent Biologics announced at the American Academy of Ophthalmology virtual meeting that IBI302, the company’s recombinant human anti-VEGF and anti-complement bi-specific fusion protein for neovascular AMD, demonstrated good safety and tolerability in a Phase I clinical trial. Read more.
Source: Innovent Biologics, November 2020
Gemini Announces Phase I Study Results
Gemini Therapeutics announced the small-scale Phase I study of GEM103, the company’s investigational treatment for dry age-related macular degeneration, met all endpoints. Results demonstrated that, in 12 patients receiving a single intravitreal injection of GEM103, no dose-limiting toxicities or treatment-related adverse events were reported. The results were presented during a virtual poster session at the 2020 American Academy of Ophthalmology virtual meeting. Read more.
SOURCE: Gemini Therapeutics, November 2020
Gyroscope Announces First Patient Dosed in HORIZON Trial
Gyroscope Therapeutics announced the first patient was dosed in the Phase II HORIZON trial evaluating GT005 in people with geographic atrophy secondary to dry age-related macular degeneration. GT005 is an investigational one-time AAV-based gene therapy. Read more.
SOURCE: Gyroscope Therapeutics, November 2020
LINEAGE PRESENTS NEW OPREGEN DATA FOR DRY AMD WITH GA
Lineage Cell Therapeutics announced positive interim results from the ongoing 24-patient Phase I/IIa clinical study of the company’s therapy, OpRegen. OpRegen is an investigational cell therapy consisting of allogeneic retinal pigment epithelium cells administered to the subretinal space for the treatment of dry age-related macular degeneration with geographic atrophy. At the American Academy of Ophthalmology virtual meeting, the company said that data showed improvements in visual acuity in cohort-four patients, with treated vs. fellow eye comparisons reaching statistical significance at nine and 12 months. Read more.
SOURCE: Lineage Cell Therapeutics, November 2020
INVESTIGATIONAL RPGR THERAPY IN X-LINKED RP PATIENTS
The Janssen Pharmaceutical Companies of Johnson & Johnson announced 12-month data from the ongoing Phase I/II trial of an investigational gene therapy for inherited retinal disease X-linked retinitis pigmentosa. They say that the results show that low and intermediate doses were well-tolerated and continued to demonstrate statistically significant sustained or increased vision improvement. Data on the novel adeno-associated virus retinitis pigmentosa GTPase regulator, jointly developed with MeiraGTx Holdings, were presented at the American Academy of Ophthalmology virtual meeting. Read more.
SOURCE: Janssen Pharmaceutical Companies of Johnson & Johnson, November 2020
ViGeneron & WuXi Strategically Partner on Gene Therapy
ViGeneron and WuXi Advanced Therapies announced a strategic partnership to accelerate development of ViGeneron’s lead product, VG901, which targets a disease gene for retinitis pigmentosa. VG901 is developed from a proprietary vgAAV vector platform that enables transduction of retinal cells. WuXi ATU will accelerate development by manufacturing, testing and making available the clinical trial-grade treatment while leveraging its AAV suspension and plasmid DNA platforms. Read more.
SOURCE: ViGeneron, WuXi ATU, December 2020
RESEARCHERS RECEIVE GRANT TO STUDY GENE ACTIVATION IN EYE DEVELOPMENT
Researchers from Florida Atlantic University’s Schmidt College of Medicine seeking to conquer a limitation in the ability to engineer tissues for regenerative therapies for age-related and degenerative diseases received a $1.3 million grant from the National Eye Institute for a project that will identify novel mechanisms for how immature eye cells activate genes to become mature visual cells. The research will be conducted in collaboration with investigators from Thomas Jefferson University in Pennsylvania. FAU researchers have discovered that specific changes in DNA conformation during tissue development regulate the activation of genes needed to make a functional eye lens through activation of novel DNA binding proteins called transcription factors. The findings will provide a basis for the development of regenerative therapies for diseases such as retinal degeneration.
SOURCE: Florida Atlantic University, October 2020
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