Survey Shows Geographic Atrophy Impact on Quality of Life

■ Results from a global survey indicate that living with geographic atrophy (GA) can cause a substantial emotional burden and impact on independence. The global Geographic Atrophy Insights Survey (GAINS), which was sponsored by Apellis Pharmaceuticals and conducted by The Harris Poll last year, included 203 adult participants with GA, in 9 countries.

According to the survey, nearly 7 in 10 of those queried believe the impact on their independence and quality of life due to their visual decline is worse than they expected; a majority of those surveyed feel the disease negatively affects their ability to read, drive, and travel; and approximately 1 in 3 had recently withdrawn from social activities because of their disease. “We conducted this survey to better understand the profound social and emotional impact of GA, and we remain committed to ensuring the patient voice is represented in our work every step of the way,” Federico Grossi, MD, PhD, chief medical officer at Apellis, said in a news release.

Phase 2b Trial Supports Safety of Oral Drug for Diabetic Retinopathy

■ Interim masked results from phase 2b of the ZETA-1 clinical study of oral APX3330 (Ocuphire) in diabetic retinopathy (DR) patients demonstrated a favorable ophthalmic and systemic safety and tolerability profile, according to lead investigator, David Boyer, MD, senior partner, Retina-Vitreous Associates Medical Group, Los Angeles, who presented the data at ARVO 2022 in Denver. Outcomes of the trial, which included 100 participants with moderately severe to severe NPDR or mild PDR (DRSS 47-61), were consistent with 11 prior safety trials of APX3330 in nonophthalmic indications, according to Dr. Boyer, who is an Ocuphire Medical Advisory Board member.

APX3330 is a novel, oral, small molecule inhibitor of Ref-1, a transcriptional regulator of key angiogenic (VEGF) and inflammatory signaling pathways relevant to retinal disease, especially DR. APX3330 is a potential alternative to intravitreal injections. The ZETA-1 trial is a randomized, placebo-controlled, double-masked, multicenter study designed to evaluate the efficacy and safety of oral APX3330 600 mg daily dose over 24 weeks in DR patients. No significant organ toxicity, vital sign abnormalities, or rash were observed. The company expects to report top-line results from the ZETA-1 trial in the second half of 2022.

Bausch + Lomb Announces US Xipere Launch and Injector Training

■ Bausch + Lomb and Clearside Biomedical announced the US launch of Xipere, triamcinolone acetonide injectable suspension, approved by the FDA for suprachoroidal use for the treatment of macular edema associated with uveitis. “Throughout the past several months, we have been training eye care professionals on how to properly administer Xipere using its unique suprachoroidal injection method, which enables targeted delivery and compartmentalization of the medication,” Joseph C. Papa, chairman and CEO of Bausch Health, said in a news release.

“Suprachoroidal administration, which provides exceptional access and high bioavailability to the posterior segment of the eye, has been well tolerated by patients. This administration technique is unlike traditional intraocular administration, therefore training on how to properly inject it is important. I encourage eye care professionals to take advantage of the training being offered by Bausch + Lomb,” Steven Yeh, MD, said in a news release. Dr. Yeh is professor of ophthalmology and director of retinal disease and uveitis at Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, and principal investigator for the Xipere phase 3 pivotal study.

SCORE2: RVO Patients Need Long-term Monitoring, Treatment

■ Five-year outcomes of the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2), published in the American Journal of Ophthalmology, revealed that treatment for retinal vein occlusion (RVO) yields long-lasting vision gains, with visual acuity remaining significantly above baseline at 5 years; however, many patients require ongoing treatment.

“While anti-VEGF therapy is associated with significant improvement in both retinal swelling and visual acuity in patients with central or hemiretinal vein occlusion, our findings show that most of the patients followed still required treatment to control the macular edema for at least 5 years,” said SCORE2 chair Ingrid U. Scott, MD, MPH, in a news release. “This demonstrates the importance of continued monitoring of these patients. Prior to this study, retinal vein occlusion was widely considered an acute illness. This study shows that RVO is a chronic disease. It also underscores the importance of disease monitoring and individualized treatment to achieve the best possible vision,” she added.

Outlook Therapeutics Submits FDA Application for Wet AMD Therapeutic

■ Outlook Therapeutics announced that it has submitted its Biologics License Application (BLA) to the FDA for ONS-5010, an investigational therapy which, if approved, will be branded as Lytenava (bevacizumab-vikg). ONS-5010 is in development to be administered as an intravitreal injection for the treatment of wet AMD and other retinal diseases. If approved, Lytenava (bevacizumab-vikg) could replace the current practice of using unapproved repackaged intravitreal bevacizumab sourced from compounding pharmacies for the treatment of wet AMD.

The BLA submission is based on the totality of data from the Outlook Therapeutics wet AMD clinical program for ONS-5010, which consists of 3 completed registration clinical trials: NORSE ONE, NORSE TWO, and NORSE THREE. “This BLA submission for our investigational ONS-5010 represents a real step forward for potentially providing an on-label, FDA-approved alternative for the most frequently used anti-VEGF treatment in wet AMD patients in the US,” said Russ Trenary, president and CEO of Outlook Therapeutics, in a news release.

Genentech Launches DME Study in Underrepresented Populations

■ Genetech announced that it has launched Elevatum, a study of Vabysmo in patients with diabetic macular edema (DME) from underrepresented patient populations. Black, African American, Hispanic, Latin American, and Indigenous people are disproportionately affected by diabetes and are at higher risk of developing DME. In recognition of this increased risk and the historical industrywide lack of diversity in clinical trials, Genentech designed Elevatum, a phase 4, multicenter, open-label, single-arm trial designed specifically to study Vabysmo in underrepresented populations.

The Elevatum study is designed to ease barriers to clinical trial participation, with a goal of better understand how traditionally underrepresented patient populations with DME respond to treatment to help deliver better, more equitable care.

“Historically, ophthalmology clinical trials focused on diabetic eye disease have been lacking representation from different ethnic and racial groups,” Manuel Amador, MD, medical director at Genentech, said in a news release. “By including a diversity of populations, perspectives, and experiences, our goal is to improve scientific understanding of DME and ultimately improve the standard of care for all patients.”

Samsara Vision to Initiate Supplemental Implantable Telescope

■ Samsara Vision announced FDA approval to initiate a US-based premarket approval supplemental study to evaluate improvements in visual acuity (VA) and the safety of its SING IMT, the Smaller-Incision New-Generation Implantable Miniature Telescope, in people living with late-stage AMD. The CONCERTO trial will recruit older adults 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 device is implanted during outpatient cataract surgery through an incision ranging from 6.5 mm to 7.5 mm. Both the operative and the nonstudy eye will be assessed preoperatively and postoperatively, over 12 months across 5 visits, at up to 20 sites across the United States.

“Clinical studies are the foundation of advancing medical breakthroughs. We look forward to sharing results from CONCERTO and working closely with the FDA to determine a timely pathway to bring the SING IMT to market in the United States,” said Samsara Vision CEO Thomas Ruggia in a news release.

Remote Monitoring Associated With Better AMD Outcomes

■ Notal Vision reported that a retrospective study of its ForeseeHome remote AMD monitoring system showed substantially better outcomes for participating patients compared to standard of care AMD monitoring. Results from the Analysis of Long-term Visual Outcomes of ForeseeHome Remote Telemonitoring (ALOFT) study were published in Ophthalmology Retina. The study followed 2,123 dry AMD patients from 5 retina practices over 10 years. Outcomes revealed that visual acuity (VA) at conversion to wet AMD was 20/39 for ALOFT patients, compared to the mean VA of 20/83 using current standard of care of office visits and patient self-reported symptoms alone. Also, patients whose conversion to wet AMD was detected early using ForeseeHome had an average VA of 20/32 after an average of 2.7 years of treatment, compared to a typical patient’s VA of 20/80 after 2 years of follow-up using current standard of care monitoring.

“We were truly amazed by the magnitude of long-term benefit for the patient population,” said ALOFT investigator Richard Garfinkel, MD, from Retina Group of Washington, in a news release.

Study Update Shows RBM-007 Effective for Treatment-naïve Wet AMD

■ Ribomic announced an update of results from its investigator sponsored trial (IST), TEMPURA, along with updated data from its TOFU and RAMEN studies with RBM-007, an investigational antifibroblast growth factor-2 aptamer, in wet AMD. RBM-007 appears effective in improving BCVA and retinal anatomy in treatment-naïve wet AMD when compared to eyes previously treated long-term with anti-VEGF agents.

The TEMPURA IST was an open-label, uncontrolled, small study (n=5) of treatment-naïve wet AMD subjects. Patients received an intravitreal injection of 2 mg RBM-007 once monthly for 3 months. The majority of subjects showed improvement in best-corrected visual acuity and/or central subfield thickness. At month 4 (study exit), 1 subject had a BCVA gain of 15 letters compared to baseline, and a CST improvement of about 200 μm. Further analysis of phase 2 TOFU data and results from the RAMEN study, in previously treated wet AMD, show no benefit of RBM-007 monotherapy or the combination over Eylea in any of the study outcome measures.

Surgeon Implants First IOPCL for Macular Degeneration

■ Harvard Eye Associates in Orange County, California, reported that it was the site of the first implantation of an AccuraSee intraocular pseudophakic contact lens (IOPCL). The implant is designed to improve near vision in patients with macular degeneration, and allows patients to use parts of the retina that are not affected by the disease. The lens is placed on top of an existing posterior chamber IOL for patients who have had previous cataract surgery. John Hovanesian, MD, the implanting surgeon, said in a news release, “This implant could permanently change the lives of patients who have serious vision loss.”

The AccuraSee implant, which was invented by Kevin J. Cady, CEO and founder of Onpoint Vision Inc, was part of a first-in-human (FIH) US Investigational Device Exemption (IDE) study evaluating the ability of the lens to improve near vision for people with macular degeneration.

Beovu Gets Second EC Stamp of Approval

■ Novartis announced that the European Commission (EC) has approved Beovu (brolucizumab) 6 mg for the treatment of visual impairment due to DME. The approval was based on year 1 data from the phase 3, randomized, double-masked KESTREL and KITE studies, which met their primary endpoint of noninferiority in change in BCVA from baseline vs aflibercept at year 1.

In both trials, more than half of patients in the Beovu 6 mg arm remained on a 12-week dosing interval through year 1. In aggregate, a numerically lower proportion of patient eyes treated with Beovu had intraretinal fluid, subretinal fluid, or both at week 52 vs eyes treated with aflibercept. “This approval marks a significant milestone for DME patients, many of whom are of working age and struggle with adherence due to the need to manage multiple comorbidities related to diabetes,” said Jill Hopkins, Novartis senior vice president and ophthalmology global development unit head, in a news release. This is the second indication for Beovu granted by the EC, which was first approved for the treatment of wet AMD in 2020.

Phase 3 Study Reveals Positive Results for Nyxol Mydriasis Reversal

■ Ocuphire Pharma announced positive top-line results in MIRA-3, the company’s second phase 3 trial investigating Nyxol for the reversal of pharmacologically induced mydriasis. Nyxol is an investigational eye drop formulation of phentolamine mesylate designed to reduce pupil size by inhibiting contraction of the iris dilator muscle.

MIRA-3, which was designed as a multicenter, randomized, parallel arm, double-masked, placebo-controlled trial, enrolled 368 subjects across 16 US sites. The trial met its primary endpoint, with 58% of subjects treated with Nyxol returning to ≤0.2 mm of their baseline PD at 90 minutes compared to only 6% of subjects treated with placebo. The effect was also significant at 60 minutes: Nyxol 42% vs placebo 2%.

“This means that that we have 2 FDA registration trials to support potential approval for the reversal of mydriasis (RM) indication. We intend to file an NDA with the US FDA in late 2022, which, if approved, would position Ocuphire for commercial launch of Nyxol in RM in the second half of 2023,” said Ocuphire Pharma president and CEO Mina Sooch, MBA, in a news release.

Vigeneron to Collaborate With Regeneron on Inherited Retinal Disease Gene Therapy

■ Vigeneron GmbH announced a strategic collaboration and option agreement with Regeneron Pharmaceuticals to develop and commercialize a gene therapy based on Vigeneron’s novel engineered recombinant adeno-associated virus vectors (vgAAVs), to treat an inherited retinal disease (IRD). Under the terms of the research collaboration, Regeneron and Vigeneron will create and validate vgAAV-based therapeutic candidates for one undisclosed IRD target. Vigeneron receives an upfront payment and research funding, and Regeneron has an option for an exclusive license to develop, commercialize, and manufacture the vgAAV-based product for the specific target. Additionally, Vigeneron is eligible to receive an option exercise fee, and development and commercial milestone payments, plus royalties on net sales.

“We are delighted to work with Regeneron to potentially provide an intravitreally delivered gene therapy for patients suffering from an inherited eye disease,” said Caroline Man Xu, MD, cofounder and CEO of Vigeneron, in a news release. “Our aim is to overcome the current limitations of gene therapy and to bring a novel therapeutic approach to patients in need,” she added.

Study Confirms Validity of At-home Visual Acuity Tests

■ Measurements for 3 different types of at-home self-administered visual acuity (VA) tests were within one line of Snellen acuity compared with in-office VA measurements, according to a study published in JAMA Ophthalmology. Kellyn N. Bellsmith, MD, and colleagues from the Casey Eye Institute at the Oregon Health & Science University, Portland, validated 3 at-home VA tests — printed chart, mobile phone app, and website — and compared them with in-office measurements of subjects with VA of 20/200 or better, from 4 ophthalmology clinics. Participants were randomly assigned to self-administer 2 of the 3 at-home tests within 3 days of their clinic visit.

One hundred twenty-one participants completed the study. The researchers found that the mean in-office VA was 0.11 logMAR (Snellen equivalent, 20/25). The mean difference between the at-home and in-office VA was −0.07, −0.12, and −0.13 for the printed test, mobile phone app, and website, respectively.

“The COVID-19 pandemic has created an opportunity for expansion of teleophthalmology services due to the necessity of limiting in-person exposures,” the authors wrote. “Validated at-home tests provide an important first step in the expansion of teleophthalmology.” This study was funded by a National Institutes of Health/National Eye Institute core grant and an unrestricted grant from Research to Prevent Blindness.

Study Reflects Association Between Retinal Vessel Density and COVID-19

■ Individuals with COVID-19 exhibited reduced retinal vessel density and elevated D-dimer levels during the acute phase of the infection, in a study designed to evaluate macular vessel density and perfusion in COVID-19 patients and investigate whether there is a correlation between retinal vascular abnormalities and clinical and laboratory parameters. The study authors reported that patients showed short-term retinal vasculature abnormalities that may be related to a prothrombotic state associated with the SARS-CoV-2 infection.

Cross-sectional analysis of 80 patients was conducted at the Hospital Clinico San Carlos, in Madrid, Spain. Patients with laboratory-confirmed COVID-19 underwent fundus examination in the emergency department, and optical coherence tomography angiography 4 weeks later. The mean age of participants was 55; 46.3% were male. Patients with D-dimer ≥500 ng/mL during SARS-CoV-2 infection had a decrease of central vessel density (mean difference 2.2; 95% CI 0.4-3.9) and perfusion density (mean difference 4.9; 95% CI 0.9-8.9) after the acute phase of COVID-19. These variations of vessel density and perfusion density were not documented in patients with lactate dehydrogenase ≥500 U/L, C-reactive protein ≥10 mg/L, and hypoxemia.

Given that “the retinal microvasculature shares many morphological and physiological properties with the vasculature of other vital organs, further research is needed to establish whether patients with increased D-dimer levels require more careful assessment and follow-up after COVID-19,” the study authors wrote. RP