DERBY and OAKS Data on Pegcetacoplan Support Long-term GA Vision Preservation

■ Apellis Pharmaceuticals released new findings from the 24-month phase 3 OAKS study of pegcetacoplan at the AAO meeting in Chicago. Post hoc analysis of microperimetry data revealed that both monthly and every-other-month (EOM) pegcetacoplan treatment preserved visual function of retinal cells near the GA lesion border compared to sham. “These results provide the first direct evidence that slowing GA lesion growth has the potential to preserve visual function. ... Combined, these data underscore the potential of pegcetacoplan to preserve vision over the long term and become the first treatment for GA.” said Charles Wykoff, MD, PhD, Retina Consultants of Texas, who presented the data.

The analysis measured the visual function of cells within 250 µm on either side of the lesion border that are at the highest risk of permanently losing VF as lesions expand. At 24 months, positive trends in microperimetry measures demonstrated that patients in both monthly and EOM pegcetacoplan treatment groups lost less retinal sensitivity compared to the sham group with increasing effects over time, and patients in both monthly and EOM pegcetacoplan treatment groups had fewer new scotomatous points compared to sham over 24 months, with increasing effects over time.

Prior to the AAO meeting, Apellis also announced 24-month pegcetacoplan lesion growth data, from the phase 3 DERBY and OAKS studies. Both monthly and EOM pegcetacoplan showed a clinically meaningful reduction in GA lesion growth from baseline compared to sham: in DERBY, 19% in the monthly group and 16% in the EOM group, and in OAKS, 22% in the monthly group and 18% in the EOM group. Between months 18 and 24, the pegcetacoplan treatment effect accelerated compared to previous 6-month periods, with robust reductions of GA lesion growth vs sham.

“Pegcetacoplan is the only treatment for GA to demonstrate increased effects on slowing lesion growth over time and a favorable safety profile in 2 large, phase 3 studies,” Federico Grossi, MD, PhD, chief medical officer of Apellis, said in a news release.

Iveric Achieves GA Therapeutic Milestone With GATHER1 and GATHER2 Outcomes

■ Top-line efficacy and safety results from GATHER2, Iveric Bio’s second phase 3 clinical trial (along with GATHER1) of avacincaptad pegol, were presented at the AAO 2022 meeting, in Chicago. Avacincaptad pegol, also known as Zimura, is an investigational complement C5 inhibitor being evaluated for the treatment of GA. Zimura met its primary endpoint of mean rate of growth (slope) in GA area at 12 months, with statistical significance and a favorable safety profile. A total of 448 participants were enrolled in this double-masked, sham-controlled study measuring the efficacy and safety of monthly 2 mg intravitreal Zimura. There were no events of endophthalmitis, no intraocular inflammation events, and no ischemic optic neuropathy events through month 12.

Iveric previously reported that, in GATHER1, Zimura met its prespecified primary efficacy endpoint with statistical significance. In GATHER1, approximately 84% of patients had lesions within 500 µm of the central subfield at baseline, and roughly 1/3 of all patients had disease within 100 µm of the foveal center point. Zimura reduced lesion growth, compared to sham, across all distances from the foveal center point.

“We are excited to have achieved something that has never been done before in GA — deliver 2 phase 3 studies that met their prespecified, primary endpoint at 12 months of slowing GA progression,” Glenn P. Sblendorio, chief executive officer of Iveric Bio, said in a news release.

Aura’s AU-011 Interim Data Reflect Significant Reduction in Tumor Growth

■ Aura Biosciences released interim phase 2 data from its study evaluating the safety and efficacy of suprachoroidal administration using its first virus-like drug conjugate product candidate, belzupacap sarotalocan (AU-011; Figure 1), for the first-line treatment of patients with early-stage choroidal melanoma. Ivana Kim, MD, MBA, director of the ocular melanoma center at Massachusetts Eye and Ear and associate professor of ophthalmology at Harvard Medical School, presented the findings at the annual AAO meeting, in Chicago.

The results, with an average of 6 months follow-up in patients that received 3 cycles of therapy, showed a statistically significant reduction in the tumor growth rate compared to each patient’s documented growth rate at study entry, and an 88.9% tumor control rate. In addition, the visual acuity preservation rate was also 88.9% in these cohorts, with the majority of patients being at high risk for vision loss with tumors close to fovea or optic disk.

“Preliminary analysis of the data from the phase 2 trial using suprachoroidal administration supports tolerability up to 3 cycles of therapy and shows a dose-dependent antitumor response. The results provide further clinical evidence to support the potential use of belzupacap sarotalocan as a novel targeted therapy in patients with early-stage disease,” Cadmus Rich, MD, chief medical officer and head of R&D for Aura Biosciences, said in a news release.

8 mg Aflibercept Meets Primary Endpoints in Pivotal DME and Wet AMD Trials

■ Regeneron Pharmaceuticals announced that it met its primary endpoints in 2 pivotal trials investigating novel aflibercept 8 mg with 12-week and 16-week dosing regimens in patients with DME and wet AMD. The PHOTON trial in DME and the PULSAR trial in wet AMD both demonstrated that aflibercept 8 mg 12-week and 16-week dosing regimens achieved noninferiority in vision gains compared to the Eylea 8-week dosing regimen. In these trials, the safety of aflibercept 8 mg was consistent with the established safety profile of Eylea. Regeneron and Bayer will submit these data to regulatory authorities in countries around the world.

“These pivotal aflibercept 8 mg trials demonstrated that nearly 90% of patients with DME and almost 80% of patients with wet AMD were able to maintain a 16-week dosing regimen,” David Brown, MD, FACS, director of research at Retina Consultants of Texas and a trial investigator, said in a news release.

Janssen Announces Late-Breaking Gene Therapy Study Findings at AAO

■ The Janssen Pharmaceutical Companies of Johnson & Johnson announced primary results from its phase 1/2 study evaluating the investigational gene therapy botaretigene sparoparvovec (formerly AAV-RPGR), in patients with X-linked retinitis pigmentosa (XLRP) associated with the RP GTPase regulator (RPGR) gene. Treatment with botaretigene sparoparvovec was found to have an acceptable safety profile, and efficacy assessments demonstrated encouraging improvements in retinal sensitivity, visual function, and functional vision. These findings and additional updates, including data from a phase 1 trial of investigational gene therapy JNJ-81201887 (JNJ-1887) for patients with GA, were presented at the annual AAO meeting, in Chicago.

In the study’s dose-escalation and expansion phases, significant sustained or increased functional improvement in each visual domain was observed in participants treated with botaretigene sparoparvovec compared to the randomized untreated control arm of the study, at 6 months post-treatment.

Janssen also presented late-breaking data from a phase 1, open-label, multicenter, dose-escalation, safety and tolerability study of a single intravitreal injection of JNJ-1887 in patients with advanced dry AMD with GA. In this study, patients (n=17) were sequentially enrolled at a low, intermediate, and high dose without steroid prophylaxis, and all 3 doses of JNJ-1887 met the primary endpoint of safety over the 2-year follow-up.

MeiraGTx and Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, are jointly developing botaretigene sparoparvovec as part of a broader collaboration to develop and commercialize gene therapies for the treatment of inherited retinal diseases.

Vabysmo’s AAO Presentations Support Its Rapid, Sustained Effect

■ Two-year data from phase 3 Vabysmo (faricimab; Genentech) trials in AMD and DME support the long-term efficacy, durability, and safety of this anti-VEGF agent, while also demonstrating its rapid and sustained effect on anatomic outcomes, according to findings presented at the annual American Academy of Ophthalmology (AAO) meeting in Chicago. Jennifer Lim, MD, director of retina at the University of Illinois in Chicago, reported 2-year results from TENAYA and LUCERNE, highlighting faster drying during the initial dosing period and revealing that the proportion of patients with no retinal fluid was greater with Vabysmo (77.2%) than with aflibercept (66.5%) through week 12.

Rishi Singh, MD, professor of ophthalmology at Cleveland Clinic’s Lerner College of Medicine, presented 2-year results from the phase 3 TENAYA and LUCERNE wet AMD trials showing early and rapid extension to 4-month dosing did not compromise visual acuity. Patients on 4-month dosing maintained stable vision gains and anatomical improvements through year 2.

Caroline Baumal, MD, professor of ophthalmology and director of the retinopathy of prematurity service at the New England Eye Center of Tufts Medical Center in Boston, presented 2-year results from YOSEMITE and RHINE, noting that the proportion of patients with absence of DME and intraretinal fluid through year 2 was greater with faricimab than with aflibercept. Additionally, more patients treated with faricimab achieved absence of DME and intraretinal fluid earlier and with fewer injections than aflibercept.

In related news, prior to AAO, Roche announced that the European Commission approved Vabysmo for the treatment of wet AMD and DME. According to a news release, faricimab is the only injectable eye medicine approved in Europe with phase 3 studies supporting treatment at intervals of up to 4 months for people living with wet AMD and DME.

Tarcocimab Shows Noninferiority to Aflibercept for RVO in the BEACON Trial

■ The latest results from the BEACON phase 3 study of tarcocimab tedromer (KSI-301; Kodiak Sciences) revealed that tarcocimab showed noninferiority to aflibercept (Eylea) for RVO. The results were presented at the AAO meeting in Chicago, by Michael Singer, MD, from Medical Center Ophthalmology Associates in San Antonio, Texas.

In this head-to-head comparison, the BEACON study included 3 parts: a matched phase (2 months), a maintenance phase (4 months), and a personalized treatment interval (6 to 18 months). Aflibercept was given monthly, while tarcocimab was dosed monthly for 2 months, then every other month until month 6. The primary endpoint was the change in visual acuity at month 6. A total of 568 patients were randomized into either the tarcocimab arm or the aflibercept arm. Both drugs improved vision and decreased CST. In terms of both VA and OCT, no significant difference was found between tarcocimab and aflibercept. Vision improved approximately 13 to 15 letters in both the tarcocimab and aflibercept arms. However, Tarcocimab was able to achieve these improvements in vision and OCT with fewer doses than aflibercept: specifically, 3.9 doses vs 5.8 doses, respectively. Even more notable, this was the first time that a drug given Q8 weeks was shown to be noninferior to monthly aflibercept in patients with RVO.

Interim Results Show OTX-TKI Achieved Stable BCVA and CST

■ Ocular Therapeutix released interim 7-month data from the phase 1 clinical trial evaluating its intravitreal hydrogel implant OTX-TKI, which is being developed for the treatment of wet AMD and other retinal diseases. The data were presented in Chicago, at the annual AAO meeting, by Dilsher Dhoot, MD, of California Retina Consultants. The interim results showed subjects treated with a single OTX-TKI implant demonstrated stable and sustained BCVA and CSFT in the OTX-TKI arm at 7 months, which was comparable with the aflibercept arm dosed every 8 weeks. The data also showed that 80% of subjects in the OTX-TKI arm were rescue free up to 6 months, and 73% of subjects in the OTX-TKI arm were rescue free up to 7 months.

“The data highlight the potential of OTX-TKI to become a highly differentiated product capable of providing a durable anti-VEGF response that improves upon today’s standard of care in the management of wet AMD and with potential in other retinal diseases. We look forward to discussing our future development plans with the FDA and, subject to those discussions, plan to initiate a phase 2 clinical trial in the third quarter of 2023,” Antony Mattessich, president and chief executive officer of Ocular Therapeutix, said in a news release.

AAO and ARVO Say the Time for Digital Imaging Standards Is Now

■ AAO and ARVO published a joint statement in the journal Ophthalmology emphasizing the importance of digital imaging standards for the advancement of research and clinical care. On behalf of their members, these associations stress that “the use of standard formats for digital imaging is in the best interests of the ophthalmic community and the patients they serve by allowing the field of ophthalmology and vision science research to progress along the path of improved electronic workflow, data interoperability, and novel artificial intelligence systems.” According to the statement, the benefits of standardized digital imaging include, “the ability to make timely and appropriate treatment decisions based on combining data from different imaging devices and the use of resources required to deliver that care,” among other things.

The statement concludes with 10 recommendations for next steps to achieve the objectives of digital image standards adoption, including that “manufacturers of imaging devices and picture archiving and communications systems (PACS) vendors provide their conformance statements to the AAO and ARVO to house in a single website for visibility and transparency.”

Novel AMD Gene Therapy Targets Malfunctioning Mitochondria

■ A novel gene therapy that targets mitochondrial function and increases energy production levels in the retina, ophNdi, has been developed by researchers at Trinity College Dublin’s School of Genetics and Microbiology. The therapy uses a virus to access the cells and provide a lifeline to malfunctioning mitochondria to enable them to generate extra energy and continue to support vision.

The therapy has shown benefit in multiple models of dry AMD, according to Jane Farrar, PhD, the study’s senior author. “This study provides the first evidence in models that directly modulating bioenergetics in eye cells can provide benefit and improve visual function in dry AMD. In doing so, the study highlights the energy powerhouses of the cell, mitochondria, as key targets for dry AMD,” Dr. Farrar said in a news release.

The research is funded by Enterprise Ireland and the European Regional Development Fund under Ireland’s European Structural and Investment Funds program.

First US Patient Receives Autologous Stem Cell Therapy for Dry AMD

■ Surgeons at NIH successfully implanted a patch of patient-derived induced pluripotent stem cells (iPS), with the goal of treating advanced dry AMD (Figure 2). This was the first time a US patient received autologous stem-cell therapy for dry AMD. The procedure was performed at the NIH Clinical Center, in Bethesda, MD, under a phase 1/2a clinical trial to determine the therapy’s safety.

The patient’s blood cells were converted to iPS cells in the NIH lab and programmed to become RPE cells, which support light-sensing photoreceptors in the retina. The iPS cell-derived therapy was developed by the Ocular and Stem Cell Translational Research Section team led by NEI senior investigator Kapil Bharti, PhD, in collaboration with Fujifilm Cellular Dynamics Inc. and Opsis Therapeutics. This work was supported by the NIH Common Fund and NEI Intramural funding.

CONCERTO Study Introduces First US SING IMT Surgeries

■ Samsara Vision announced the completion of the first US surgeries of its SING IMT (Smaller-Incision New-Generation Implantable Miniature Telescope), as part of the CONCERTO clinical study, to evaluate improvements in VA and safety of the device in people living with late-stage AMD. The SING IMT is a Galilean-style telescope implant that is implanted during cataract surgery with a corneal incision range of 6.5 mm to 7.5 mm. Images seen in straight-ahead vision are magnified 2.7 times and projected onto healthy, undamaged areas of the macula in the back of the eye, reducing the apparent impact of AMD on central vision. The CONCERTO trial will recruit 100 adults with stable, bilateral central scotomas due to late-stage AMD and fovea-involving GA or disciform scar to receive a SING IMT in 1 eye.

“It’s highly encouraging that our first surgeries went smoothly. We look forward to working with the eye health community across the country during the CONCERTO study,” Thomas Ruggia, CEO of Samsara Vision, said in a news release.

Heru Introduces Dark Adaptation to Vision Screening Platform

■ Heru announced that it has launched dark adaptation, the newest modality for its interactive wearable augmented reality/virtual reality (AR/VR) vision-screening platform. Dark adaptation measures the eye’s ability to adjust from light to dark environments. Impaired dark adaptation may be one of the earliest indicators of AMD. Early detection of AMD is key to preserving visual function, and most patients do not seek treatment until it is too late. Heru’s vision-screening platform (Figure 3) leverages contrast sensitivity and dark adaptation allowing for earlier intervention and management of the disease.

“We are incredibly pleased to announce the release of dark adaptation, further advancing our platform and delivering on our commitment to establish a comprehensive wearable AMD portfolio,” Mohamed Abou Shousha, MD, PhD, CEO and founder of Heru, said in a news release. Dark adaptation has multiple supported ICD-10 codes, and is co-billable with visual fields, OCT, fundus imaging, and/or office visits.

B+L Report Highlights AMD “Blind Spots” and Need for Education

■ A survey of US adults revealed that 81% would be willing to forgo highly valued commodities, experiences, and capabilities — such as use of the internet, going on a vacation, or even the ability to remember people’s names — if it meant never losing their eyesight. Despite this prioritization of the ability to see, only 37% of US adults aged 50 or over know that AMD is the leading cause of vision loss for Americans. These findings are from Bausch + Lomb Corporation’s recently released first annual Visionary Report, which was designed to identify key insights into the value Americans place on their eyesight, as well as the “blind spots” that may exist in the understanding and awareness of AMD.

Among the report’s notable findings: 75% of Americans who see an ophthalmologist or optometrist and have heard of AMD have never discussed it with their provider. “Our hope is that this report will raise awareness, help to fill those education gaps, and foster important dialogue between eye care professionals and their patients,” Joe Gordon, president of Global Consumer, Surgical and Vision Care for Bausch + Lomb, said in a news release.

IrisVision CEO Launches Radius XR Assistive Device Company

■ IrisVision cofounder and CEO Ammad Khan introduced a new company, Radius XR. Radius XR leverages its core technology of the same name to create a patient-guided exam process that facilitates the diagnosis of a range of pervasive vision problems in the United States, according to the press release. Specifically, using a Radius XR headset (Figure 4), patients can self-perform such tests as visual field, visual acuity, contrast sensitivity, and more. RP