FDA Grants Priority Review to Pegcetacoplan GA Therapy

■ Apellis Pharmaceuticals announced that the FDA has granted priority review designation to its New Drug Application (NDA) for intravitreal pegcetacoplan C3 therapy for GA. The NDA is based on results from the phase 3 DERBY and OAKS studies at 12 months and 18 months and the Phase 2 FILLY study at 12 months. In these studies, both monthly and every-other-month pegcetacoplan resulted in a clinically meaningful reduction of GA lesion growth and a favorable safety profile.

“Both monthly and every-other-month pegcetacoplan meaningfully slowed GA disease progression across three large studies, and the potential approval of this medicine would be a breakthrough for patients,” Charles Wykoff, MD, PhD, OAKS study investigator and director of research at Retina Consultants of Texas, said in a news release. Apellis plans to submit a marketing authorization application to the European Medicines Agency in the second half of 2022.

DORC Gets FDA Market Clearance for First Eva Nexus Retinal Injector

■ DORC International announced that it received 510(k) market clearance from the FDA for Eva Nexus, the first system approved for subretinal injection. The Eva Nexus includes a trocar cannula and a microinjection system designed for precise, ±1 psi control of injections of less than 1 mL.

“I am confident that [Eva Nexus] will deliver next generation fluidics, IOP control, and vitrectomy efficiency,” said Asheesh Tewari, MD, Michigan Retina Center, in a news release. “For the past 6 months I have been using DORC’s new trocar cannula system that features the Hi-Flow infusion line for superior flow rates and redesigned cannula for improved postoperative wound sealing. These infusion improvements will be critical to match the increased aspiration flow rates achieved by the addition of a new TDC Veloce cutter.”

Eylea Extended Dosing Regimen Accepted for FDA Review

■ Regeneron Pharmaceuticals announced the FDA has accepted for review the Eylea (aflibercept) injection supplemental Biologics License Application (sBLA) for an every-16-week 2-mg dosing regimen, after initial monthly doses, in patients with diabetic retinopathy (DR). Eylea was originally approved for the treatment of all stages of DR, with a dosing regimen of every 4 or 8 weeks, after 5 initial monthly doses.

The sBLA is supported by data from the phase 3 PANORAMA trial investigating every 8- and 16-week Eylea dosing regimens vs sham, in patients with severe nonproliferative DR without diabetic macular edema (DME). The submission was further supported by data from the NIH-sponsored Protocol W trial investigating an Eylea every-16-week dosing regimen, in patients with moderate to severe nonproliferative DR without center-involved DME vs sham.

At 1 year, PANORAMA met its primary endpoint of proportion of patients with ≥2-step improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. At 2 years, in both the PANORAMA and Protocol W trials, a greater proportion of patients receiving Eylea every 16 weeks experienced a ≥2-step improvement in DRSS score, along with greater reductions in the risk of developing vision-threatening complications vs sham.

Vabysmo Study: Inhibition of Ang-2 and VEGF-A Leads to Durable Efficacy

■ Genentech announced new 2-year data from the TENAYA and LUCERNE studies that reinforce the long-term efficacy, safety, and durability of Vabysmo (faricimab-svoa) in patients with wet AMD. The data, which were presented at the 2022 annual meeting of the American Society of Retina Specialists, revealed that more than 60% of people receiving Vabysmo could be treated every 4 months while achieving comparable vision gains vs aflibercept given every 2 months, and nearly 80% of people receiving Vabysmo could be treated every 3 months or longer. Patients treated with Vabysmo received a median number of 10 injections over 2 years vs 15 injections for patients treated with aflibercept.

In related news, early data from the ongoing TRUCKEE study comprising mostly patients who require frequent injections to address persistent disease activity associated with neovascular AMD show that BCVA improved slightly in patients in whom retinal fluid persisted despite previous treatment. Patients had been treated previously with aflibercept (Eylea; Regeneron) in more than half of cases, followed by ranibizumab (Lucentis; Genentech), and brolucizumab (Beovu; Novartis). In other study news, 2-year outcomes from the YOSEMITE/RHINE faricimab studies of DME patients revealed the number of patients in the faricimab personalized treatment interval arms who achieved Q12W or Q16W dosing at week 52 maintained extended dosing at week 52. Overall, these studies illustrate that dual inhibition of Ang-2 and VEGF-A with faricimab may result in stabilized vessels and reduced neovascularization, leading to durable efficacy when treating retinal diseases.

Outlook Therapeutics to Resubmit Lytenava BLA to FDA

■ Outlook Therapeutics released an update regarding the status of its Biologics License Application (BLA) submission for ONS-5010/Lytenava, (bevacizumab-vikg) for the treatment of wet AMD. The BLA for ONS-5010 was originally submitted to the FDA in March 2022 and subsequently voluntarily withdrawn in May 2022 to provide additional information requested by the FDA. Following receipt of further correspondence from the FDA, Outlook Therapeutics has confirmed the additional information necessary to resubmit the BLA.

“The additional correspondence from the FDA confirms our commitment to our shareholders to resubmit a completed BLA to FDA by [end of] September of this year,” said C. Russell Trenary, President and CEO of Outlook Therapeutics, in a news release.

DRCR Trial Finds Step Therapy Effective for DME

■ Clinical trial results from the DRCR Retina Network suggest that a step strategy, in which patients with diabetic macular edema (DME) start with a less expensive medicine and switch to a more expensive medicine if vision does not improve sufficiently, gives results similar to starting off with the higher-priced drug. The study enrolled 270 participants with DME, who had BCVA between 20/50 and 20/320. Participants received either Avastin (bevacizumab; Genentech) or Eylea (aflibercept; Regeneron) injections every 4 weeks for 24 weeks. If eyes assigned to Avastin failed to reach the preset improvement benchmarks starting at 12 weeks, the eye was switched to Eylea. After 24 weeks, injection frequency could be tapered to maintain VA. After 2 years, eyes in both groups had similar VA outcomes, improving on average approximately 3 lines on an eye chart. In the Avastin group, 70% of eyes switched to Eylea during the study.

“Insurance companies often require clinicians to start with the less expensive treatment, so we wanted to see how a specific treatment strategy using this approach would affect patient care,” said lead study author Chirag Jhaveri, MD, Austin Research Center for Retina, Texas, in a news release.

Affordable Care Act Did Not Decrease Emergency Eyecare Visits

■ A study to investigate the association between the Affordable Care Act and nationwide eye-related emergency department (ED) utilization revealed that the ACA did not decrease ED usage for eye care, but the percentage of uninsured patients accessing eye care in the ED did decrease from 19% to 14.3%. Researchers from the Yale School of Medicine used data from the US Nationwide Emergency Department Sample to analyze eye-related ED visits before and after the ACA was mandated. ED visits were categorized as emergent, nonemergent, or indeterminate. Overall, there were 16,808,343 eye-related ED visits during the study period from 2010 to 2017, with 8,088,203 visits occurring before the ACA was mandated (2010-2013) and 8,720,766 visits after the ACA was mandated (2014-2017).

The study authors concluded in their paper published in Ophthalmology that “a significant proportion of ED visits continue to be for nonemergent ophthalmic conditions, which can be managed in the outpatient setting. This results in more costly and less specialized care [and] additional measures beyond expanding insurance coverage may be necessary to provide high quality, efficient and equitable outpatient ophthalmic care to all Americans.”

Aura Reports Top-line Data from Choroidal Melanoma Retrospective Study

■ Aura Biosciences reported results from a retrospective, matched-case control study comparing visual acuity outcomes for 43 patients from its phase 1b/2 trial evaluating intravitreal administration of belzupacap sarotalocan in patients with early-stage choroidal melanoma to 150 patients from a published study evaluating plaque radiotherapy treatment for small choroidal melanoma. Belzupacap sarotalocan achieved statistically significant vision preservation compared to plaque radiotherapy, which is the current standard of care. The loss of vision in radiotherapy patients was ≥3 lines in a majority of patients.

“Being able to treat the disease early, avoid radiotherapy, and spare long-term vision loss in many patients, as well as potentially reducing the risk of metastatic disease, could represent a paradigm shift in our approach to the treatment of choroidal melanoma. This would be a significant improvement in the quality of life for patients with this life-threatening rare disease,” said Carol Shields, MD, chief of the ocular oncology service at Wills Eye Hospital and professor of ophthalmology at Thomas Jefferson University, Philadelphia, in a news release.

Eyepoint Announces Positive 12-Month Data From Phase 1 DAVIO

■ Eyepoint Pharmaceuticals announced 12-month data from the phase 1 Durasert and Vorolanib in Ophthalmology (DAVIO) clinical trial evaluating EYP-1901, a sustained delivery anti-VEGF therapy targeting wet AMD, as a potential every-6-month treatment. The final 12-month data from the phase 1 DAVIO clinical trial showed no reports of ocular SAEs or drug-related systemic SAEs. Additionally, updated data from the 12-month follow-up confirm stable BCVA (-4.12 ETDRS letters), stable central subfield thickness on OCT (-2.76 μm), and an expected late increase in supplemental anti-VEGF therapy given the insert’s expected drug depletion, with 35% of eyes supplement free up to 12 months vs 53% supplement free up to 6 months.

“The final 12-month results from the DAVIO clinical trial highlight EYP-1901’s continued positive safety and efficacy profile with promising durability as a potential every-6-month maintenance therapy for previously treated wet AMD,” said Rishi Singh, MD, a member of Eyepoint’s scientific advisory board, in a news release. RP

First SING IMT Surgeries for AMD Performed in FDA Study

Samsara Vision announced the completion of the first Smaller-Incision New-Generation Implantable Miniature Telescope (SING IMT) surgeries in the United States. The surgeries were part of a US Food and Drug Administration (FDA) clinical study, CONCERTO, to evaluate visual acuity (VA) improvements and device safety in patients with late-stage age-related macular degeneration (AMD). David RP Almeida, MD, MBA, PhD, of Erie Retinal Surgery in Pennsylvania, and Marc H. Levy, MD, of the Sarasota Retina Institute in Florida, performed the first US SING IMT procedures.

The SING IMT is a Galilean-style telescope implanted during outpatient cataract surgery with a corneal incision range between 6.5 mm and 7.5 mm. Images seen in “straight-ahead” vision are magnified 2.7x and projected onto healthy, undamaged areas of the macula, reducing the impact of the AMD “blind spot” on central vision. The CONCERTO trial will recruit 100 adults aged 65 and older living with stable (nonactive neovascularization), bilateral central scotomas due to late-stage AMD, and fovea-involving geographic atrophy or disciform scar to receive a SING IMT in 1 eye.

“The SING IMT procedure allowed for not only a smaller corneal incision, but also a consistent and predictable insertion of the device,” Dr. Levy said in a news release.

Subretinal Drusenoid Deposits Strongly Associated With Vascular Disease

Patients who have AMD with subretinal drusenoid deposits (SDD) are at high risk for vascular disease, whereas their counterparts who have drusen are not, according to a study performed by researchers at New York Eye and Ear Infirmary of Mount Sinai. This study is the first to demonstrate a link between SDD and vascular disorders. Of the 126 study participants, 62 had SDD and 64 had drusen. Patients with a history of cardiovascular disease or stroke were 3 times more likely to have SDD than patients without. The researchers suggested that underlying heart and vascular disease likely compromises blood circulation in the eye, leading to SDDs beneath the retina and ultimately causing vision loss and blindness.

“If ophthalmologists diagnose or treat someone with the SDD form of AMD, but who otherwise seems well, that patient may have significant undetected heart disease, or possibly carotid artery stenosis that could result in a stroke,” lead author R. Theodore Smith, MD, PhD, a professor of ophthalmology at the Icahn School of Medicine at Mount Sinai, said in a news release. “In the future, such patients will be considered for early referral to a cardiologist for evaluation and possibly treatment.”

Iveric Bio and Delsitech Enter Zimura Development Agreement

Iveric Bio and Delsitech announced an exclusive global license agreement providing Iveric Bio with the right to develop and commercialize new formulations of Zimura (avacincaptad pegol) using Delsitech’s silica-based sustained-release technology. Iveric Bio is developing sustained-release technologies for the treatment of AMD. Iveric Bio previously announced that GATHER1, the company’s first phase 3 clinical trial of Zimura for GA, met its prespecified primary efficacy endpoint with statistical significance.

“We are thrilled to collaborate with the Delsitech team on investigating additional sustained-release formulations for Zimura, with their drug-delivery expertise and advanced technology, and look forward to evaluating a sustained release formulation in GA and potentially earlier stages of AMD,” said Pravin U. Dugel, MD, president of Iveric Bio, in a news release.

Kubota Announces End of Stargardt Disease Phase 3 Clinical Trial

Kubota Vision announced the completion of the phase 3 clinical trial investigating emixustat hydrochloride in patients with macular atrophy secondary to Stargardt disease. The study was a multicenter, randomized, double-masked, placebo-controlled phase 3 clinical study in which subjects were randomly assigned to emixustat 10 mg or placebo in 2 to 1 ratio, once daily for 24 months. The target number of subjects was 162; however, due to high interest in the study, 194 subjects were enrolled across 29 sites, in 11 countries.

The primary objective of this study was to determine if emixustat reduces the rate of macular atrophy progression, in comparison to placebo, in subjects with Stargardt disease. Secondary objectives include assessing changes in visual field (VF) parameters such as best corrected visual acuity (BCVA) letter score and reading speed. In a news release, Ryo Kubota, MD, PhD, the chairman, president, and CEO of Kubota Vision, said, “We are looking forward to receiving the results of the trial in the coming months.”

LIGHTSITE III Data Show Improvements in Intermediate Dry AMD

Lumithera announced findings from LIGHTSITE III, its study of dry AMD subjects treated with photobiomodulation (PBM) using the Valeda Light Delivery System. Results from the prospective, double-masked, randomized, multicenter clinical trial demonstrated statistically significant improvement in the prespecified primary endpoint in BCVA at 13 months in the PBM treatment group over the sham-treatment group. In the PBM treatment group, 55% of the subjects showed a ≥5 letter improvement, with a mean of 9.7 letters and 26% achieved a ≥10 letter improvement, with a mean of 12.8 letters.

“The safety results from the LIGHTSITE III trial through the 13-month time point were excellent,” stated René Rückert, MD, MBA, the chief medical officer of LumiThera, in a news release. “We will continue to follow all patients for the full 24 months for safety.”

Meiragtx Study Demonstrates Safety and Improvement in XLRP

Meiragtx Holdings announced top-line data from MGT009, its phase 1/2 clinical study of botaretigene sparoparvovec (formerly referred to as AAV-RPGR), an investigational gene therapy in development for the treatment of patients with X-linked retinitis pigmentosa (XLRP), with disease-causing variants in the RPGR gene.

Treatment with botaretigene sparoparvovec was found to be generally safe and well tolerated, and significant improvements were demonstrated in retinal function, visual function, and functional vision in comparison to the randomized untreated control arm of the study, at 6 months after treatment. Improvements were demonstrated in retinal sensitivity on static perimetry, functional vision in a vision-guided mobility assessment, and other measures of visual function and functional vision, including VA using ETDRS and patient-reported outcome measures.

“These data give us increased confidence in the potential for botaretigene sparoparvovec to meaningfully improve the lives of the thousands of patients with XLRP,” said Alexandria Forbes, PhD, president and chief executive officer of Meiragtx, in a press release.

NEI Study Finds Loss of “Youth” Protein May Drive Aging in the Eye

Loss of the protein pigment epithelium-derived factor (PEDF), which protects retinal support cells, may drive age-related changes in the retina, according to a new study in mice from the National Eye Institute (NEI), part of the National Institutes of Health (NIH). This finding could lead to therapies to prevent AMD and other age-related retinal conditions.

To examine the retinal role of PEDF, NEI scientists studied a mouse model that lacks the PEDF gene (Serpinf1). They found that the RPE cell nuclei were enlarged, which may indicate changes in how the cells’ DNA is packed. The RPE cells also had turned on four genes associated with aging and cellular senescence, and levels of the PEDF receptor were significantly below normal. Furthermore, unprocessed lipids and other photoreceptor outer segment components had accumulated in the RPE layer of the retina.

“We always wondered if loss of PEDF was driven by aging or was driving aging. This study, especially with the clear link to altered lipid metabolism and gene expression, indicates the loss of PEDF is a driver of aging-related changes in the retina,” said Patricia Becerra, PhD, chief of NEI’s section of protein structure and function and senior author of the study, in a news release.

Studies Support Efficacy of Notal Vision Remote OCT Monitoring

Notal Vision reported that numerous studies support the feasibility and efficacy of its Notal Home OCT device, which is part of a comprehensive remote monitoring service that includes a monitoring center and artificial intelligence algorithms for information processing. One prospective and cross-sectional study of 333 wet AMD patients and 600 eyes demonstrated that more than 91% of patients were able to successfully acquire images without technician assistance. The imaging showed excellent correlation with in-office OCT for detecting the presence of fluid, with over 95% agreement. Additionally, a prospective and longitudinal study demonstrated proficient self-imaging capability, with 2,300 scans taken at a 95% success rate. In another study where compliance was analyzed, patients performed an average of 5.8 exams per week, a rate that ensures any exudation of fluid was promptly captured.

“We are excited to see multiple investigators evaluating different aspects of our investigational Home OCT platform. This is further validation of the efficacy of our digital health-based remote monitoring model,” said Kester Nahen, PhD, the CEO of Notal Vision, in a news release.

Oculis Announces First Patient Enrolled in Phase 3 OPTIMIZE Trial

Oculis announced that the first patient has been enrolled in its phase 3 OPTIMIZE (Once-daily Post–ocular surgery Treatment for Inflammation and pIan to MinimIZE drops) trial evaluating the efficacy and safety of once-daily OCS-01, a novel, high concentration, preservative-free, topical formulation of dexamethasone for the treatment of inflammation and pain following cataract surgery. OPTIMIZE is a randomized, double-blind, placebo-controlled phase 3 trial being conducted in 25 participating sites across the United States, and it is scheduled to enroll approximately 240 patients. Efficacy measures of the trial include the absence of anterior chamber cells at day 15 and absence of pain at day 4.

OCS-01 has been developed using Oculis’s Optireach solubilizing nanoparticle technology, a proprietary platform that enables the formulation of drugs as noninvasive topical eyedrop treatments. This allows a longer residence time on the eye surface and enhances their bioavailability in the relevant eye tissues, particularly the retina.

Olix Submits IND Application for Gene Therapy for Advanced AMD

Olix Pharmaceuticals announced that it submitted an Investigational New Drug (IND) application to the FDA for OLX10212, an RNA interface (RNAi) therapeutic, for the treatment of advanced AMD. The objective of this phase 1 multisite study is to determine the safety and tolerability of OLX10212 in patients with advanced AMD.

“We are excited about this submission to the FDA because it presents as an important milestone not only for Olix, but also for the entire field of RNAi therapeutics development, as it is the first ophthalmic RNAi therapeutics entering the clinical stage since 2015,” said Dong Ki Lee, PhD, founder and chief executive officer of Olix Pharmaceuticals, in a news release.

Although RNAi technology has achieved success in the treatment of liver diseases, its application to extrahepatic organs is still in its infancy, according to Dr. Lee. In 2020, Olix entered a licensing agreement with Théa Open Innovation, a French company dedicated to ophthalmology, to transfer the worldwide rights (excluding Asia-Pacific) to eye disease treatment programs, including OLX10212.

Second Sight Announces Continued NIH Funding of Orion Study

Second Sight Medical Products announced that it received notice from the NIH of the release of year 4 funding for the early feasibility clinical trial for the continuation of its research and testing for the Orion Visual Cortical Prosthesis. The NIH released $1.1 million of the $6.4 million planned 5-year grant. The early feasibility study of the Orion prosthesis is currently under way at the Ronald Reagan UCLA Medical Center in Los Angeles, California, and the Baylor College of Medicine in Houston, Texas.

Leveraging Second Sight’s 20 years of experience in neuromodulation for vision, the Orion Visual Cortical Prosthesis System is an implanted cortical stimulation device intended to provide useful artificial vision to individuals who are blind due to a wide range of causes, including glaucoma, diabetic retinopathy, eye injury, and optic nerve injury or disease. Orion is intended to convert images captured by a miniature video camera mounted on glasses into a series of small electrical pulses. The device is designed to bypass diseased or injured eye anatomy and to transmit these electrical pulses wirelessly to electrodes implanted on the surface of the brain’s visual cortex, where it is intended to provide the perception of patterns of light.

Archway Trial Measures CST During Anti-VEGF Maintenance Phase

The phase 3 randomized active control ARCHWAY Trial to evaluate the safety and efficacy of the Port Delivery System (PDS) with ranibizumab (Susvimo; Genentech) for the treatment of neovascular AMD demonstrated that PDS with ranibizumab efficiently controlled retinal fluctuations and maintained vision over 96 weeks.

The aim of the ARCHWAY trial was to assess relationships between central subfield thickness (CST) fluctuations and VA in patients with wet AMD treated with either PDS (an FDA-approved drug delivery system consisting of an ocular implant designed to deliver a customized formulation of ranibizumab into the vitreous) or monthly intravitreal ranibizumab injections.

The frequency of clinically significant fluctuation events that occurred between baseline and week 96 was similar in the PDS and monthly ranibizumab arms, but fewer than one-third of the patients had such events, indicating good control of disease activity regardless of study arm. Eyes with CST fluctuations had marginally lower VA outcomes at week 96 compared with eyes that did not have fluctuations. The findings were presented at the 40th annual meeting of the American Society of Retina Specialists, held in New York City during July 2022.

Survey Demonstrates Degree of Burnout Among US Ophthalmologists

A survey to determine the prevalence of physician burnout among ophthalmologists in the United States, and to identify associated risks, found that 37.8% of respondents self-reported symptoms of occupational burnout. Among those surveyed, gender, practice type, and employment autonomy were the highest risk factors. The survey, which was facilitated by researchers at Tulane University Medical School, was distributed through email listservs to several national ophthalmology societies.

Of the 592 ophthalmologists responding to the survey, 37.8% (224) self-reported symptoms of burnout. Vitreoretinal specialists were the least likely to experience burnout, with 12 of 39 (30.8%) reporting symptoms, while uveitis specialists had the greatest likelihood, with 30 of 66 (45.4%) reporting symptoms of burnout. Of all the 224 physicians who reported burnout, 65.2 percent had mild symptoms, followed by 29.5% with moderate symptoms and 5.4% experiencing severe burnout. Women were almost twice as likely to report burnout. Physicians employed in academic and hospital facilities reported higher rates of burnout compared with those in large private groups. Burnout was associated with self-reported low work control, insufficient time for documentation, and misalignment with departmental leaders.

Brolucizumab Meets Primary Outcomes Midway Through TALON AMD Trial

The 32-week primary outcomes of the phase 3b TALON matched treat-and-extend study analyzing the efficacy and safety of brolucizumab vs aflibercept in nAMD patients were presented at the American Society of Retina Specialists 2022 annual meeting by Carl Regillo, MD, of Wills Eye Hospital and Mid-Atlantic Retina. The study aimed to evaluate whether brolucizumab (Beovu; Novartis) is superior to aflibercept (Eylea; Regeneron) in extending duration of the treatment intervals by analyzing the distribution of the last treatment interval with no disease activity up to week 32. TALON’s second objective was assessing noninferior visual outcome of brolucizumab relative to aflibercept, with the endpoint of mean change in BCVA from baseline at weeks 28 and 32.

Brolucizumab met both primary endpoints: Brolucizumab was found to be superior to aflibercept in the distribution of the last treatment interval and noninferior in visual outcome. Additionally, brolucizumab achieved greater reduction in central subfield thickness from baseline at weeks 28 and 32 compared to aflibercept. In his presentation, Dr. Regillo noted that 64-week end-of-study results, which may help clarify how these drugs can be extended over time, will be available later this year.

Bausch + Lomb Receives Permanent J-Code for Injectable Xipere

Bausch + Lomb announced that the Centers for Medicare and Medicaid Services (CMS) issued a permanent J-Code, J3299, for Xipere (triamcinolone acetonide injectable suspension) that became effective for provider billing on July 1. Xipere (Bausch + Lomb/Clearside Biomedical) was approved by the FDA last year, and is the first and only therapy available in the United States that utilizes the suprachoroidal space to treat patients who have macular edema associated with uveitis. “The issuance of the permanent J-Code will help facilitate access to Xipere for Americans suffering from macular edema associated with uveitis and help streamline the reimbursement process,” said Yolande Barnard, senior vice president and general manager of US Pharmaceuticals for Bausch + Lomb, in a press release. Physicians interested in attending a Xipere training session can register at https://www.xipere.com/hcp/xipere-training .