Subretinal Drusenoid Deposits Associated With Heart Disease and Stroke

■ Patients who have AMD with subretinal drusenoid deposits (SDD) are at significant risk for cardiovascular disease and stroke, according to a New York Eye and Ear Infirmary of Mount Sinai study published in Retina. This study is the first to demonstrate a link between the disorders. The researchers suggested that underlying heart and vascular disease likely compromise blood circulation in the eye, leading to the SDDs beneath the retina and ultimately causing vision loss and blindness.

“We believe poor ocular circulation that causes SDDs is a manifestation of underlying vascular disease. This has important public health implications and can facilitate population screening and disease detection with major impact,” author Jagat Narula, MD, PhD, associate dean of global affairs and professor of medicine (cardiology), and radiology, at the Icahn School of Medicine at Mount Sinai, said in a news release.

This study was funded by a Regeneron Pharmaceuticals Investigator-initiated Study, Research to Prevent Blindness Challenge Grant, Macula Foundation, Bayer-Global Ophthalmology Award, and International Council of Ophthalmology-Alcon Fellowship.

Apellis Submits Phase 3 Data to the FDA for Pegcetacoplan NDA

■ Apellis Pharmaceuticals submitted 24-month efficacy data from the phase 3 DERBY and OAKS studies to the FDA in support of its New Drug Application for pegcetacoplan, for the treatment of geographic atrophy. The data showed robust and consistent effects with monthly and every-other-month pegcetacoplan treatment in both studies. The 24-month safety data were previously submitted as part of the 120-day update. The more recent submission is a major amendment to the NDA, extending the review period by 3 months, with an expected Prescription Drug User Fee Act (PDUFA) target action date in February.

“Assuming a February PDUFA date, we would be prepared to launch immediately following an approval,” Cedric Francois, MD, PhD, Apellis CEO and cofounder, said in a news release.

Salvat Laboratories Submits NDA to FDA for Nanoemulsion Corticosteroid

■ Salvat Laboratories submitted a New Drug Application to the FDA for clobetasol nanoemulsion for the treatment of inflammation and pain after ocular surgery. The formulation was shown to be safe and effective in 2 phase 3 clinical trials. The clinical trials, which were conducted in the United States, involved 426 cataract surgery patients; 281 received clobetasol and 145 received a placebo. Study results showed a total absence of inflammation after the first 7 days of treatment, increased efficacy in absorption, no blurred vision or discomfort after application, low impact on IOP, and no rebound effects in the 2 weeks after a standard 14-day course of treatment, thus eliminating the need for dosage tapering toward the end of treatment.

The nanoemulsion technology, IMPACT-SVT, delivers the lowest drug concentration by dissolving clobetasol in nanodroplet. The treatment is the first ocular corticosteroid formulated in a nanoemulsion.

Alimera Supports DRCR Retina Network’s Radiation Retinopathy Research

■ Alimera Sciences will provide Iluvien (fluocinolone acetonide 0.19 mg) sustained release intravitreal implants for a randomized clinical trial evaluating intravitreal faricimab (6.0 mg) injections or fluocinolone acetonide (0.19 mg) intravitreal implants vs observation for prevention of VA loss due to radiation retinopathy. The initiative is the result of an agreement between Alimera and the Jaeb Center for Health Research Foundation Inc. (JCHR) on behalf of the DRCR Retina Network.

The study is set to include 600 participants with primary choroidal melanoma receiving treatment with plaque brachytherapy. “We are very excited to be working with this prestigious network of physicians in evaluating Iluvien’s potential to address another unmet need affecting the retina. When utilized as baseline therapy, as in our New Day Study for DME, we believe Iluvien’s continuous microdosing delivery may prevent, delay, or reduce the occurrence of radiation retinopathy and consequent vision loss when used in patients treated with plaque brachytherapy,” Rick Eiswirth, Alimera President and CEO, said in a news release.

Regenxbio Announces Positive Interim RGX-314 Trial Data

■ Regenxbio reported positive outcomes of ongoing clinical trials of RGX-314 for the treatment of wet AMD, including interim data from the expansion of phase II AAVIATE — which added a sixth cohort to evaluate RGX-314 at the third dose level of 1x10¹² GC/eye with a short course of prophylactic ocular steroids to evaluate the ability to prevent or reduce the occurrence of mild-to-moderate intraocular inflammation.

RGX-314 continues to be well tolerated in 85 patients from cohorts 1 to 5, and there has been a meaningful reduction in treatment burden at 6 months across all dose levels. Among the noteworthy outcomes: 67% of patients in cohort 4 were injection free, and there were no meaningful differences in outcomes at 6 months for patients who are NAb positive. Interim data from cohort 6 indicates that an 85% reduction in treatment burden was observed at the third dose level, with short-course prophylactic ocular steroids following RGX-314 administration.

“RGX-314 continues to be well tolerated, with emerging evidence of treatment effect, including meaningful reduction in anti-VEGF treatment burden at all dose levels. We look forward to expanding this trial to further explore the third dose level,” said Regenxbio chief medical officer Steve Pakola, MD, in a news release.

Outlook Therapeutics and AmerisourceBergen Plan Potential Lytenava Launch

■ Outlook Therapeutics and AmerisourceBergen have entered into a strategic relationship in preparation of the anticipated US commercial launch of Lytenava (ONS-5010/bevacizumab-vikg), an investigational intravitreal injection for the treatment of wet AMD and other retinal diseases, if approved by the FDA.

“AmerisourceBergen will provide expansive reach and access to the vast majority of anti-VEGF providers. Together, we believe we will be in a position to significantly upgrade treatment options for people living with wet AMD,” C. Russell Trenary, III, president and CEO of Outlook Therapeutics, said in a news release.

In related news, the FDA has accepted for filing a Biologics License Application (BLA) for ONS-5010 and has set a Prescription Drug User Fee Act (PDUFA) goal date of August 29, 2023.

“This BLA acceptance and PDUFA date are significant milestones in our mission to offer clinicians and their patients the first and only on-label, ophthalmic bevacizumab to treat wet AMD,” Trenary said in a news release.

Aldeyra Achieves Primary Endpoint in Part 1 of Phase 3 Trial of ADX-2191

■ Aldeyra Therapeutics announced that it has achieved the primary endpoint in part 1 of its phase 3 GUARD trial of intravitreally injected ADX-2191 (methotrexate injection, USP1), an investigational drug candidate, for the prevention of proliferative vitreoretinopathy (PVR). Part 1 of the GUARD trial was designed to assess the preliminary activity of ADX-2191 vs historical control and routine surgical care without therapy in patients with PVR. Sixty-eight patients received ADX-2191, and 38 patients received routine surgical care. Relative to historical control, statistically significant reduction in retinal detachment over 6 months was observed following serial intravitreal injection of ADX-2191.

“The recent reports describing the activity of methotrexate in preventing PVR, in conjunction with the results of the GUARD trial, offer hope to many patients and physicians that today have few options for treatment,” Marco Zarbin, MD, PhD, professor and chair of the institute of ophthalmology and visual science, Rutgers New Jersey Medical School, said in a news release.

Positive Results in Leber Congenital Amaurosis Trial Announced

■ Atsena Therapeutics announced positive results from its phase 1/2 clinical trial of ATSN-101, an investigational gene therapy product formerly known as SAR439483, for the treatment of GUCY2D-associated Leber congenital amaurosis (LCA1). The data demonstrated that subretinal delivery of ATSN-101 was well tolerated and patients treated with the highest dose (1.0 x 10¹¹ vg/eye) saw clinically meaningful improvements in vision, as measured by full-field stimulus testing and multiluminance mobility testing, at more than 1 month after treatment. Patients in this cohort demonstrated a significantly larger mean change from baseline in retinal sensitivity and a trend toward a larger mean change in BCVA in treated eyes as compared with untreated eyes.

“Patients with LCA1 have profound visual impairment or blindness at birth, but their retinal structure remains intact, which indicates an opportunity to confer meaningful improvements following delivery of a subretinal gene therapy such as ATSN-101,” Kenji Fujita, MD, chief medical officer of Atsena Therapeutics, said in a news release.

Topline Phase 3 Results Show Vabysmo Improved Vision for RVO Patients

■ Genentech announced positive topline results from two global phase 3 studies, BALATON and COMINO, evaluating the bispecific antibody Vabysmo (faricimab-svoa), in macular edema due to branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). The BALATON study is being conducted in 553 people with BRVO and the COMINO study is being conducted in 729 people with CRVO or hemiretinal vein occlusion. Both studies met their primary endpoints, showing that people with ME due to BRVO and CRVO receiving Vabysmo injections every 4 weeks, for up to 24 weeks, achieved noninferior visual acuity gains compared to those receiving aflibercept injections every 4 weeks. Vabysmo also showed rapid drying of retinal fluid from baseline through week 24, and in both studies, Vabysmo was generally well tolerated and exhibited a safety profile consistent with previous trials.

“These results add to the extensive evidence supporting Vabysmo’s efficacy in treating multiple types of retinal conditions. We look forward to submitting these data to regulatory authorities,” Levi Garraway, MD, PhD, CMO and Genetech head of global product development, said in a news release.

Samsung Bioepis Presents Phase 3 Data From Ophthalmology Biosimilar Studies

■ Samsung Bioepis presented data from its ophthalmology biosimilar products at the 2022 AAO meeting in Chicago. SB15, a proposed biosimilar to aflibercept (Eylea; Regeneron), showed equivalent efficacy and comparable safety, immunogenicity, and pharmacokinetics profile to reference aflibercept in the phase 3 study interim analysis. The primary endpoint was met in terms of change from baseline in BCVA at week 8, and the 32-week interim analysis demonstrated comparability in other secondary efficacy endpoints.

A post hoc analysis of the phase 3 study of SB11, a biosimilar referencing ranibizumab (Lucentis; Genentech) indicated that immunogenicity response (incidence of antidrug antibodies) was low and not different between SB11 and reference ranibizumab. Another post hoc analysis of the phase 3 study on SB11 found that baseline age, best-corrected visual acuity, and central subfield thickness were determined to be predictive of visual acuity and anatomic outcomes when treating neovascular age-related macular degeneration with SB11 or reference ranibizumab.

“We hope that our continued efforts for data generation help ophthalmologists have better understanding of biosimilars, and their comparable efficacy, safety, immunogenicity, and PK profile to reference products,” Jin Ah Jung, director and medical affairs group leader, Samsung Bioepis, said in a news release.

Pixium Vision Publishes Paper on Prima System in Dry AMD

■ Pixium Vision announced the publication of a paper outlining further data from a study of its Prima System, a photovoltaic substitute of photoreceptors providing simultaneous use of the central prosthetic and peripheral natural vision, implanted in human patients with atrophic dry AMD to partially restore their vision. The key takeaway from the study, which was published in the Journal of Neural Engineering, is that the surgical delivery of the photovoltaic subretinal implant led to a stable retinal thickness over 36 months with no adverse structural or functional events after causing minor retinal thickness changes that settle after 3 months.

“The data in this paper further demonstrate the stability and minimal impact of the implant once in position,” Lloyd Diamond, Pixium Vision CEO, said in a news release.

Study Says US Ophthalmology Residency Programs Rank Last for Diversity

■ A UC Davis Health study on the racial and ethnic composition of residency programs in the United States found ophthalmology programs rank last in underrepresented minority group recruitment compared to other specialties. “Trends in Racial Diversity among United States Ophthalmology Residents,” was published in Ophthalmology.

According to the study, underrepresented minorities made up about 19% of medical school attendees but only 6.3% of ophthalmology residency programs. Nationwide, underrepresented minority groups comprise only 7.2% of practicing ophthalmologists in the United States.

“Our study shows the field of ophthalmology does not reflect our country’s diversity. We know from previous research that a diverse physician workforce that reflects our patient population can lead to decreased health care disparities, enhanced access to care, and improved patient outcomes and satisfaction,” Parisa Emami-Naeini, MD, MPH, assistant professor at the UC Davis department of ophthalmology and vision sciences and senior author of the study, said in a news release.

KYS Vision Publishes Remote Retina Monitoring Study Results

■ KYS Vision published clinical trial results from a study of its Macustat macular function scan for the remote monitoring of central retinal function, in the journal Digital Health. In the study, 50 eyes were evaluated with the self-administered Macustat test and compared to office-based retinal examination, which included OCT imaging of the retina. With the self-test, 96% of eyes registered central retina acuity within 0.2 logMAR of office acuity measurement, while the performance efficacy for the detection of macular function defects such as metamorphopsias and scotomas exceeded 90%.

“The Macustat test of central retinal function delivered via a telemedicine platform demonstrates high concordance with clinical findings from the in-office retina exam. I see enormous applications of such digital health tools not only for patient care, but for population health initiatives where exponential technology can deliver both scale and access,” Ranya Habash, MD, assistant professor of ophthalmology and medical director of technology innovation at Bascom Palmer Eye Institute and study coauthor, said in a news release.

FDA Grants Breakthrough Therapy Designation for Zimura for Geographic Atrophy

■ Iveric Bio announced that the FDA granted breakthrough therapy designation for avacincaptad pegol (ACP) also known as Zimura, a novel investigational complement C5 inhibitor, for the treatment of GA secondary to age-related macular degeneration. To date, ACP is the first and only investigational therapy to receive breakthrough therapy designation status for this indication. The designation was based on the 12-month primary efficacy endpoint data from the GATHER1 and GATHER2 pivotal studies, which evaluated the safety and efficacy of ACP in patients with GA located inside and/or outside of the clinical fovea.

“In both GATHER1 and GATHER2, avacincaptad pegol consistently showed a treatment effect with the first measurement at month 6 that was persistent and continued to increase over time, with observed efficacy rates of up to 35%,” said Pravin U. Dugel, MD, president of Iveric Bio, in a news release, adding, “We believe ACP has the potential to safely and effectively preserve central vision by saving photoreceptor cells for patients living with this life-changing disease that leads to irreversible blindness.”

EyeArt AI Detects DME With Greater Sensitivity Than Dilated Exams

■ A study comparing the EyeArt (Eyenuk) artificial intelligence system to dilated eye exams performed by ophthalmologists for the detection of diabetic macular edema found that dilated exams by ophthalmologists are better at ruling out disease but that EyeArt is much better at identifying patients with disease.

The study, titled “Artificial Intelligence Detection of Diabetic Retinopathy: Subgroup Comparison of the EyeArt System with Ophthalmologists’ Dilated Exams,” evaluated the sensitivity and specificity of the EyeArt system and dilated eye exams performed by general ophthalmologists and retina specialists against the rigorous ETDRS clinical reference standard on the same cohort of 521 study participants. The ETDRS reference standard was established by experts at the University of Wisconsin Reading Center using 10 fundus images per eye captured after dilation by certified photographers, whereas the EyeArt system analyzed only 2 images per eye, typically without dilation. Sensitivity was 96.4% for the EyeArt system in identifying more-than-mild DR (mtmDR), while that of ophthalmologists’ dilated exams was 27.7% on the identical cohort of study participants. Specificity was 99.6% by ophthalmologists’ dilated exams compared to 88.4% with the EyeArt system.

Intravitreal Conbercept Injections Superior to Laser in DME

■ As-needed intravitreal injections of conbercept (KH902, Chengdu Kanghong Biotech Co.) resulted in improved BCVA in patients with diabetic macular edema (DME) and were superior to results achieved with laser photocoagulation, according to results of the Sailing study, and a follow-up extension study, published in the British Journal of Ophthalmology. Researchers reported that the mean best-corrected visual acuity (BCVA) improved significantly by 8.2 letters from baseline to month 12 in the eyes treated with sham laser photocoagulation followed by as-needed 0.5-mg conbercept intravitreal injections. In contrast, the eyes treated with laser photocoagulation followed by as-needed sham intravitreal injections had an improvement of 0.3 letter.

The Sailing study was a 12-month, 18-center, randomized, double-masked, double-sham, parallel-controlled, phase 3 trial that was conducted by Chinese and American researchers in China. A 12-month, open-label extension study followed. After being switched to conbercept, in the extension study, the patients treated with laser photocoagulation followed by as-needed sham intravitreal injections had a marked improvement in BCVA. Lead authors Kun Liu, MD, and Hanying Wang, MD, concluded that as-needed intravitreal conbercept injections improved the BCVA of patients with DME, and that the drug’s efficacy was superior to that of laser photocoagulations.

Kubota Reports Positive Phase 3 Post Hoc Data on Stargardt

■ Kubota Vision announced positive results from post hoc analysis of the phase 3 clinical trial of its investigational visual cycle modulator emixustat hydrochloride, in patients with Stargardt disease. 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. Previously announced top-line results showed that the study did not achieve its preplanned primary or secondary endpoints. A multifactor analysis was performed on the subgroup of subjects with smaller lesions at baseline, controlling for the baseline factors identified in univariate and multifactor analyses to affect lesion progression in this subgroup. This analysis determined that emixustat treatment resulted in a 40.8% reduction in lesion progression compared to placebo at month 24. “We are very excited to see strong efficacy in this subgroup,” said Ryo Kubota, MD, PhD, chairman, president, and CEO of Kubota Vision, in a news release, adding, “This offers the potential to treat these patients proactively with the goal to preserve vision.”

Visibly Receives FDA Clearance for Online VA Test

■ Visibly announced that it has received 510(k) clearance from the US Food and Drug Administration for its Visibly Digital Acuity Product (VDAP), making it the first online VA test available to consumers in the United States. Consumers can access Visibly’s on-demand, self-administered VA test using a combination of a touchscreen mobile device and computer connected to the internet. The test takes 6 minutes, and results are made available to eye care providers.

“Our performance data, including our prospective, multicenter, clinical study that evaluated the safety and effectiveness of VDAP compared to an ETDRS VA lane test, demonstrated that the safety and effectiveness of VDAP are substantially equivalent to those of its predicate device. VDAP’s clinical performance will aid eye care professionals in the remote evaluation of VA and connect patients with care in a way that was not available before,” Paul Foley, Visibly COO, said in a news release.

Neurotech Reports Positive Phase 3 Macular Implant Study Results

■ Neurotech announced that it achieved positive topline results in 2 replicative phase 3 clinical trials with its investigational encapsulated cell therapy (ECT), for the treatment of macular telangiectasia type 2 (MacTel), a progressive degenerative macula disease. The multicenter, randomized, sham-controlled studies demonstrated statistical significance for the prespecified primary endpoint, and rate of change in ellipsoid zone (EZ) area loss from baseline through 24 months. The rate of change in area loss translates to and demonstrates a change in the rate of photoreceptor loss, specifically 56.4% rate of reduction in Protocol A (P<.0001) and 29.2% rate of reduction in Protocol B (P=.021).

The investigational NT-501 implant is a tiny hollow cylindrical membrane that encapsulates human epithelial cells genetically engineered to continuously produce ciliary neurotropic factor, a protein clinically validated to slow the progression of MacTel.

“The positive study results increase the confidence of our innovative ECT platform technology to deliver a novel biological agent over an extended period of time to slow the progression of retinal-based diseases,” Thomas Aaberg Jr., MD, chief medical officer of Neurotech, said in a news release. RP

Iveric Bio Completes NDA Submission to FDA for Avacincaptad Pegol for Geographic Atrophy

By Jennifer Ford, senior managing editor

Iveric Bio has submitted the third and final part of its New Drug Application (NDA) to the US Food and Drug Administration (FDA) for avacincaptad pegol (ACP), a novel investigational complement C5 inhibitor for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Per the company’s agreement with the FDA for rolling NDA review, part 3 of the NDA included chemistry, manufacturing, and controls data. There is currently no FDA approved treatment for GA.

“We are excited to have submitted our complete NDA for avacincaptad pegol with a request for priority review based on our Breakthrough Therapy designation,” said Glenn P. Sblendorio, chief executive officer of Iveric Bio, in a news release.

ACP is a novel complement C5 protein inhibitor. Overactivity of the complement system and the C5 protein are suspected to play a critical role in the development and growth of scarring and vision loss associated with GA secondary to AMD. By targeting C5, ACP has the potential to decrease activity of the complement system that causes the degeneration of retinal cells and potentially slow the progression of GA.

The NDA submission is based on the 12-month prespecified primary efficacy and safety results from the GATHER1 and GATHER2 clinical trials. ACP is the only investigational product for treatment of GA to achieve the prespecified 12-month primary endpoint in 2 phase 3 pivotal trials with observed efficacy rates of up to 35%. In addition, ACP is the first and only investigational therapy to receive Breakthrough Therapy designation for GA secondary to AMD.

ACP met its primary endpoint in the completed GATHER1 clinical trial and the ongoing GATHER2 clinical trial both of which are randomized, double-masked, sham-controlled, multicenter phase 3 clinical trials. These clinical trials measured the efficacy and safety of monthly 2 mg intravitreal administration of ACP in patients with GA secondary to AMD. For the first 12 months in both trials, patients were randomized to receive either ACP 2 mg or sham monthly. There were 286 participants enrolled in GATHER1 and 448 participants enrolled in GATHER2. The primary efficacy endpoints in both pivotal studies were based on GA area measured by fundus autofluorescence at baseline, month 6, and month 12. The mean rate of growth (slope) in GA area from baseline to month 12 using observed data was 35% in GATHER 1 and 18% in GATHER2. In GATHER1 and GATHER2 combined, the most frequently reported treatment emergent adverse events in the 2 mg recommended dose were related to injection procedure. The most common adverse reactions (≥5% and greater than sham) reported in patients who received avacincaptad pegol 2 mg were conjunctival hemorrhage (13%), increased intraocular pressure (9%), and choroidal neovascularization (7%). After 18 months of treatment in GATHER1 and 12 months of treatment in GATHER2, there were no events of serious intraocular inflammation, vasculitis, or endophthalmitis.

“We are thrilled with the statistically significant efficacy and consistent safety results from both the GATHER1 and GATHER2 pivotal clinical trials,” said Pravin U. Dugel, MD, president of Iveric Bio. “Our Special Protocol Assessment Agreement for GATHER2, rolling review, Breakthrough Therapy designation, and priority review request are intended to expedite the review process and get avacincaptad pegol to GA patients, who currently have no treatment options. We look forward to collaborating with the FDA throughout the NDA review process.”