Researchers Map Retina Changes Corresponding to Early Alzheimer Disease

■ Cedars-Sinai investigators have produced the most extensive analysis to date of changes in the retina that correspond to brain and cognitive changes in patients with Alzheimer disease. Their analysis, published in Acta Neuropathologica, is a seminal step toward understanding the effects of Alzheimer disease on the retina, especially at the earliest stages of cognitive impairment.

Investigators looked at retinal and brain tissue samples collected over 14 years from 86 human donors. They compared samples from donors with normal cognitive function to those with mild cognitive impairment at the earliest stages of Alzheimer disease as well as those with later-stage Alzheimer disease dementia. Their findings include: an overabundance of amyloid beta 42 protein, which in the brains of Alzheimer disease patients forms plaques that disrupt brain function; an accumulation of amyloid beta protein in ganglion cells; and a higher number of astrocytes and microglia immune cells tightly surrounding amyloid beta plaques.

“These findings may eventually lead to the development of imaging techniques that allow us to diagnose Alzheimer disease earlier and more accurately and monitor its progression noninvasively by looking through the eye,” Maya Koronyo-Hamaoui, PhD, professor of neurosurgery, neurology, and biomedical sciences at Cedars-Sinai and senior author of the study, said in a news release.

Aviceda Submits Investigational New Drug Application for GA Therapy

■ Aviceda Therapeutics announced that it has submitted an Investigational New Drug (IND) application to the FDA for AVD-104, a novel glycan-coated nanoparticle, for the treatment of geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). This represents a major step toward initiation of phase 2 human clinical studies for AVD-104, which is the first potential therapy for patients with GA secondary to AMD that addresses the underlying causes of the disease.

“With only 1 currently approved therapy for the treatment of GA, there is still a significant unmet medical need for patients with this condition. This IND application brings us a step closer to bringing a new and differentiated treatment option for disease modification of the key underlying pathobiology of AMD via the modulation of immune and complement dysfunction,” Mohamed Genead, MD, cofounder, CEO, and president of Aviceda, said in a news release. The company submitted a Fast Track Designation application, as suggested by the FDA.

Aviceda previously announced the successful completion of Good Laboratory Practice toxicity studies that showed positive safety data for multiple well-tolerated doses of AVD-104. This included dose-range finding studies in nonhuman primates and rabbits to support continued development and the initiation of human clinical trials.

Cognition Therapeutics to Develop Oral Drug for GA Secondary to Dry AMD

■ Cognition Therapeutics announced that its IND application for the investigation of CT1812 for GA secondary to dry AMD has been cleared by the FDA. CT1812 is an experimental orally delivered small molecule designed to penetrate the blood-brain and blood-retina barriers and bind selectively to the sigma-2 receptor complex.

Cognition plans to initiate the phase 2 MAGNIFY trial of CT1812 this year, in individuals with dry AMD who have measurable GA. The MAGNIFY study is a randomized, placebo-controlled phase 2 trial expected to enroll approximately 246 people who have been diagnosed with dry AMD with measurable GA. Over the treatment period, change in GA lesion size and BCVA, as well as other measures of safety and efficacy, will be assessed to determine if treatment can slow vision loss.

“We believe that CT1812’s oral systemic delivery combined with its potential to protect the retinal pigment epithelium (RPE) from damage, in both the affected and fellow eyes, may represent a significant advantage to the millions of people with dry AMD who are at risk for permanent vision loss,” said Anthony Caggiano, MD, PhD, Cognition’s chief medical officer and head of R&D, in a news release.

EyePoint and Rallybio Announce Research Collaboration

■ EyePoint Pharmaceuticals and Rallybio Corporation announced a research collaboration to evaluate sustained delivery of Rallybio’s inhibitor of complement component 5 (C5) using EyePoint’s proprietary Durasert technology for sustained intraocular drug delivery. The initial focus will be on GA. Under the terms of the partnership, EyePoint and Rallybio will collaborate to explore and assess the viability of utilizing Rallybio’s C5 inhibitor in EyePoint’s Durasert technology, with the intention to expand the collaboration upon mutual agreement following the evaluation.

“Geographic atrophy associated with dry macular degeneration is a devastating eye disease, and the inhibition of complement is a proven treatment pathway. We hope to leverage our Durasert technology in this collaboration to create a potential best-in-class, long-acting intravitreal insert, which we believe could provide a more desirable option for patients given that the existing approved therapy is injected every 1 to 2 months,” Jay Duker, MD, president and chief operating officer of EyePoint Pharmaceuticals, said in a news release.

EyePoint Completes Enrollment in Phase 2 of DAVIO 2 Clinical Trial

■ EyePoint Pharmaceuticals announced it has completed enrollment in the Phase 2 Durasert and Vorolanib in Ophthalmology 2 (DAVIO 2) clinical trial evaluating EYP-1901 as a potential 6-month maintenance treatment for wet AMD. The trial exceeded its original target of 144 patients, enrolling a total of 160 patients. All patients were previously treated with a standard-of-care anti-VEGF therapy and were randomly assigned to 1 of 2 doses of EYP-1901 or to an aflibercept on-label control.

Positive safety and efficacy data from the DAVIO phase 1 clinical trial showed a positive safety profile with stable visual acuity and OCT. What’s more, 53% and 35% of eyes did not require any supplemental anti-VEGF injections up to 6 and 12 months, respectively, following a single dose of EYP-1901.

“The compelling phase 1 DAVIO results demonstrate EYP-1901’s potential to transition a majority of patients to an every-6-month treatment for wet AMD, representing a ‘treat to maintain’ therapeutic approach that uses EYP-1901 as a baseline therapy following the use of large molecule anti-VEGFs with the goal of significantly extending the patient’s treatment interval,” Jay Duker, MD, president and chief operating officer of EyePoint Pharmaceuticals, said in a news release. Top-line data from the phase 2 DAVIO 2 trial are anticipated in the fourth quarter of 2023.

GenSight Biologics Publishes 5-Year Lumevoq Safety Data

■ GenSight Biologics announced the publication of pooled safety data from 5 clinical studies with lenadogene nolparvovec (Lumevoq) in the American Journal of Ophthalmology. The data confirm the good overall safety profile of lenadogene nolparvovec in terms of systemic and ocular tolerability, as well as humoral and cellular immune response, and highlight a comparable safety profile for unilaterally and bilaterally treated patients.

The authors analyzed safety data collected from ND4-LHON patients who received single unilateral or bilateral intravitreal injections of lenadogene nolparvovec across 5 clinical studies (REVEAL, RESCUE, REVERSE, RESTORE, and REFLECT). This analysis constitutes the largest cohort of ND4-LHON patients studied after gene therapy treatment. Almost all patients (95%) received lenadogene nolparvovec at a dose of 9x10¹⁰ viral genomes per eye and 88% had at least 2 years of follow-up.

“Given the good safety profile demonstrated, we believe lenadogene nolparvovec is proving itself as a potential new treatment solution for ND4-LHON patients as a clinically relevant patient benefit has been established with minimal safety risks,” Catherine Vignal-Clermont, MD, lead author of the article, said in a news release.

Iveric Bio Presents Vision Loss Reduction Data From GATHER at ARVO

■ Iveric Bio announced an exploratory time-to-event analysis from the avacincaptad pegol (ACP) GATHER clinical trial program evaluating reduction in vision loss with ACP 2 mg vs sham treatment. The GATHER1 and GATHER2 clinical trials were designed to evaluate the rate of GA lesion growth in patients with GA secondary to age-related macular degeneration (AMD). The post hoc analysis for vision loss from these pivotal studies signals up to a 59% reduction in rate of vision loss with ACP 2 mg compared to sham treatment at 12 months. Vision loss in this analysis was defined as a loss of ≥15 letters (EDTRS) in BCVA from baseline measured at any 2 consecutive visits up to month 12. Results were presented at the annual Association for Research in Vision and Ophthalmology (ARVO) meeting in New Orleans.

Results were consistent in the GATHER1 and GATHER2 clinical trials independently, signaling a 44% reduction and a 59% percent reduction, respectively, in the rate of vision loss with ACP 2 mg compared to sham over the first 12 months of treatment. In a combined analysis of GATHER1 and GATHER2, patients treated with ACP 2 mg experienced a 56% reduction in the rate of vision loss compared to sham over the first 12 months of treatment.

OliX Doses First Patient in RNAi Therapeutic Trial for AMD

■ OLiX Pharmaceuticals announced that the first patient has been successfully dosed in a phase 1 clinical trial evaluating OLX10212, an investigational RNAi therapeutic intended for the treatment of AMD, including geographic atrophy and neovascular AMD. A total of 60 patients have been enrolled in this US multicenter, multidose, dose escalation trial.

“This is a landmark study of RNA interference–based gene silencing technology in AMD that targets a novel pathway. The asymmetric siRNA technology of OLX10212 targets pathways upstream of VEGF and offers increased specificity over conventional siRNA, having the additional benefit of impermanence over gene therapy. Through both its mechanism of action and novel target, OLX10212 aims to confer efficacy coupled with extended durability beyond simply blockade of VEGF, addressing key components shared between neovascular AMD and dry AMD to the benefit of our patients,” Demetrios Vavvas, MD, PhD, scientific advisory board member for OliX Pharmaceuticals and professor of ophthalmology and director of the retina service at Harvard Medical School, said in a news release.

Awareness and Use of Ophthalmic Biosimilars are Lagging

■ Biosimilars are best known as an avenue to improve patient access and drive down the cost of high-priced biologics; however, the ranibizumab biosimilars that gained FDA approval last year — Byooviz and Coherus (Biogen) and Cimerli (Biosciences) — have not picked up traction in the ophthalmic community, according to market research company Spherix Global. A key difference between the biosimilar brands is that Cimerli gained approval for neovascular AMD and diabetic macular edema (DME), while Byooviz and Coherus are approved for neovascular AMD only.

Biosimilars have been available in the immunology and oncology communities in the United States for years, but they are new to ophthalmologists. In the first 6 months of ophthalmic biosimilar availability, awareness and familiarity are marginal, and willingness to prescribe is low, according to a survey of ophthalmologists administered by Spherix Global. Nearly one-quarter of ophthalmologists surveyed were unaware of Byooviz’s launch and another one-third were unaware of Cimerli’s. Among the ophthalmologists surveyed, only 1 in 5 reported any use of the biosimilars, and roughly one-quarter of nonusers reported they do not intend to try the biosimilar agents. Meanwhile, those who have prescribed the biosimilars say they are reasonably satisfied with the therapies.

Study Shows High Sensitivity of Flavoprotein Fluorescence at Detecting Retinal Disease

■ OcuSciences announced publication of a study showing that flavoprotein fluorescence (FPF) can detect retinal diseases with a high degree of sensitivity despite variations in structural retinal findings. The study, published in Frontiers in Ophthalmology, was led by Richard Rosen, MD, chief of the retina service and vice chair and director of ophthalmology research at New York Eye and Ear Infirmary of Mount Sinai.

This cross-sectional observational study included 88 eyes, with cohorts of retinal vein occlusion (RVO), diabetic retinopathy (DR), exudative age-related macular degeneration (exudative AMD), and central serous retinopathy (CSR). Patients were imaged with OcuScience’s OcuMet Beacon between October 2021 and August 2022 to capture and measure their overall FPF intensity and FPF heterogeneity. The OcuMet Beacon is an automated, rapid retinal imager that assesses mitochondrial function by interrogating flavoproteins and uses specific spectral signatures and advanced software to help clinicians identify early markers of disease. Patients in all 4 cohorts were shown to have significantly elevated FPF measures.

“These findings suggest that FPF is a robust and reliable measure when investigating retinal diseases,” Dr. Rosen said in a news release.

LumiThera Shows Sustained Vision Improvement in US LIGHTSITE III Trial

■ LumiThera announced 24-month data from its LIGHTSITE III multicenter clinical trial, which demonstrated sustained vision improvement in patients with dry AMD who received treatment with the Valeda Light Delivery System, a photobiomodulation (PBM) device.

LIGHTSITE III was conducted at 10 US retinal centers and enrolled 100 subjects with early to intermediate dry AMD. Eyes were treated with the Valeda system every 4 months. In the PBM arm there was a statistically significant visual acuity improvement at month 21 following the last treatment, with sustained vision benefits throughout the trial including the 24-month trial end.

The trial initially demonstrated sustained and statistically significant improvement in the primary endpoint, BCVA, at 13 months in the PBM group compared to the sham group. Now, a sustained, mean increase in the ETDRS score of >5.0 letters from baseline is reported at both the 13-month and 21-month time points, and improvement from baseline in BCVA at 24 months in the PBM group was significantly greater than in the sham group, with 5.9 vs 1.0 letters.

“These results confirm the multicenter European LIGHTSITE II trial and extend the improvements to 2 years,” René Rückert, MD, MBA, chief medical officer for LumiThera, said in a news release. The sustained >5 letter improvement for 24 months was outstanding considering the earlier stage of AMD disease and the good BCVA at baseline in these patients.”

Study Shows Ocular Implant Dosing Noninferior to Ranibizumab Injections

■ Two-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD) demonstrated treatment with PDS Q24W provided vision and anatomic outcomes comparable with monthly intravitreal ranibizumab through almost 2 years, with 2 refill-exchanges per year. Archway was a Phase 3, randomized, multicenter, open-label, active-comparator trial.

PDS Q24W was found to be noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 60/64 and 88/92 of +0.4 (95% confidence interval [CI], –1.4 to +2.1) and –0.6 ETDRS letters (95% CI, –2.5 to +1.3). Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events (AEs) of special interest were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. The most common AE of special interest reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations.

Study Shows LTFU in Wet AMD Patients Treated With Anti-VEGF Injections

■ Nearly 1 out of 9 patients with wet AMD treated with anti-VEGF injections are lost to follow-up (LTFU), while 1 out of 7 patients are nonpersistent, according to a retrospective cohort study using IRIS (Intelligent Research in Sight) Registry data. The study cohort was composed of 156,327 treatment-naïve patients with wet AMD who were subsequently treated with anti-VEGF therapy from 2013 to 2015 and followed through 2019. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Loss to follow-up was defined as no follow-up within 12 months from last intravitreal injection. Nonpersistence was defined as no follow-up within 6 months from last intravitreal injection.

For wet AMD, 11.6% (95% CI, 11.4-11.7) of patients were LTFU and 88.4% of patients had a follow-up within 12 months. Odds of LTFU for Black or African American patients (OR, 1.32; 95% CI, 1.08-1.61; P=.007) were greater than for White patients. Odds of LTFU were higher for patients with Medicaid insurance (OR, 1.27; 95% CI, 1.01-1.60; P=.04) and lower for patients with Medicare Fee-for-Service insurance (OR, 0.69; 95% CI, 0.64-0.74; P<.001) compared to patients with private insurance.

Ocugen IND Application Initiates Phase 1 Trial of OCU200 for DME

■ Ocugen announced that it has submitted an IND application to the FDA to initiate a phase 1 clinical trial of OCU200, a fusion protein with a distinct mechanism of action, for the treatment of diabetic macular edema (DME). This action fulfills the company’s commitment to file the IND for OCU200 within the first quarter of 2023.

The planned phase 1 clinical study will assess the unilateral intravitreal administration of OCU200 alone or in combination with an approved anti-VEGF therapy in participants with DME. This is a multicenter, open-label, dose-ranging study with 3 cohorts in the dose-escalation portion of the study and 1 cohort in the combination therapy portion of the study.

Submitting the IND application “is an important step toward fulfilling our mission to bring novel therapeutics to address limitations of the current standard of care or unmet medical needs in hard-to-treat blindness diseases,” Arun Upadhyay, PhD, chief scientific officer at Ocugen, said in a news release. He added, “We are encouraged by the potential for OCU200 to provide a new treatment option for the significant percentage of people living with DME, including nonresponders to the current standard of care.”

EyeBio Introduces Executive Team and Shares Clinical Trial Plans

■ EyeBio announced several appointments to its executive team, and shared an update about Restoret, its trispecific Wnt agonist antibody designed to address unmet needs in posterior segment eye disease. Anthony P. Adamis, MD, has been appointed Chief Scientific Officer. Dr. Adamis, who cofounded EyeBio in 2021 and Eyetech in 2002 with David Guyer, MD, previously served as senior vice president of product development and development innovation at Genentech, a member of The Roche Group. In addition to Dr. Adamis, EyeBio appointed Loni Da Silva as chief regulatory officer; Frances Betts as global head, clinical operations; Mike Davies, as chemistry, manufacturing, and control (CMC) lead; and Eric Ng, PhD, as senior vice president, biology.

“The world-class team we have assembled gives us the talent and resources to continue our rapid progress and success in advancing a strong pipeline. It is a privilege to be surrounded by an elite group of leaders in ophthalmology, many of whom have been working in this space since the dawn of pharmacotherapy for eye disease,” EyeBio CEO and president Dr. Guyer said in a news release.

The EyeBio team plans to file for clinical trial authorizations to enable a global phase 1b/2 clinical trial of Restoret in the second quarter of 2023. Restoret previously demonstrated efficacy in preclinical ophthalmic models, including validation in genetic models. RP