Pegcetacoplan Shows Continued GA Reduction

■ Apellis Pharmaceuticals announced that the phase 3 DERBY and OAKS studies showed that investigational intravitreal pegcetacoplan continued to reduce geographic atrophy (GA) lesion growth and demonstrate a favorable safety profile at month 18 for the treatment of GA secondary to age-related AMD. These data will be included in the New Drug Application (NDA) that the company plans to submit to the FDA in the second quarter of 2022.

“Pegcetacoplan is the only therapy to continuously reduce GA lesion growth across a large and broad patient population in phase 3 studies,” Federico Grossi, MD, PhD, chief medical officer at Apellis, said in a news release.

The reduction in GA lesion growth improved with monthly pegcetacoplan treatment from 13% to 21% from months 0 to 6 to months 12 to 18. The reduction in GA lesion growth improved with every-other-month pegcetacoplan treatment from 12% to 17% from months 0 to 6 to months 12 to 18. In a news release, Jeffrey S. Heier, MD, of Ophthalmic Consultants of Boston, said, “These results provide further evidence that pegcetacoplan meaningfully slows disease progression and has the potential to preserve vision longer.” Dr. Heier is principal investigator of the DERBY study.

Pivotal Faricimab Studies Published in The Lancet

■ Two papers highlighting 1-year results from 4 pivotal phase 3 studies of Genentech’s faricimab (Vabysmo) were published in The Lancet. Faricimab, an investigational bispecific antibody, was approved by the FDA in January for the treatment of wet AMD and DME. All 4 studies — which enrolled more than 3,000 people — met their primary endpoints, showing that patients treated with faricimab up to every 4 months achieved noninferior vision gains compared to aflibercept given every 2 months. About half of eligible faricimab patients were able to go 4 months between treatments in the first year, and approximately three-quarters could go 3 months or longer in the TENAYA and LUCERNE wet AMD studies and the YOSEMITE and RHINE DME studies.

“These data ... reinforce the potential of faricimab as an important treatment option that may help improve and maintain vision while extending the time between treatments up to four months,” said Levi Garraway, MD, PhD, Genentech chief medical officer and head of global product development, in a news release. Faricimab is the first bispecific antibody for the eye, targeting and inhibiting 2 distinct pathways linked to a number of vision-threatening retinal conditions by neutralizing angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A).

New Vabysmo and Susvimo Data Support Vision Maintenance Potential

■ Genentech announced new 2-year data from its phase 3 studies of Vabysmo (faricimab-svoa) and Susvimo (ranibizumab injection) for intravitreal use via ocular implant. In the YOSEMITE and RHINE studies, DME patients received Vabysmo, either every 2 months or up to every 4 months, or aflibercept every 2 months. Two-year results showed Vabysmo patients maintained the vision improvements achieved in the first year and vision gains continued to be noninferior to those achieved by aflibercept patients. In YOSEMITE, the average vision gains from baseline at 2 years were +10.7 eye chart letters in both the Vabysmo treat-and-extend and 2-month arms, and +11.4 letters in the aflibercept arm. In RHINE, the average vision gains from baseline at 2 years were +10.1 and +10.9 letters in the Vabysmo treat-and-extend and 2-month arms, respectively, and +9.4 letters in the aflibercept arm.

In the Archway study, wet AMD patients received either Susvimo refilled every 6 months or monthly ranibizumab 0.5 mg eye injections. Two-year results showed vision was maintained by Susvimo patients and continued to be noninferior to that achieved with monthly ranibizumab injections. Susvimo patients averaged -1.1 eye chart letters in visual acuity from baseline at 2 years, whereas monthly ranibizumab patients averaged -0.5 letters from baseline.

Iveric Bio Announces GATHER1 Foveal Anatomy Post Hoc Analysis

■ Iveric Bio performed a post hoc analysis of GA growth parameters to explore the rate of disease progression within various regions in the fovea in a subset of patients from the GATHER1 Zimura (avacincaptad pegol) phase 3 clinical trial. In the analysis, a reduction in lesion growth in 5 standardized regions surrounding and including the central foveal area was observed for patients receiving Zimura 2 mg as compared to patients receiving sham over 18 months. The results of this subgroup analysis are consistent with the primary analysis results in the intent-to-treat population. The post-hoc analysis evaluated GA growth in 5 standardized regions in the retina for patients for whom images were available at relevant time points (n=47 in the Zimura 2 mg group and n=79 in the sham group).

“This analysis supports our expectation [of] a greater reduction in growth away from the foveal center, reflecting the circumferential growth pattern typical for GA patients. We believe the observed pattern of reduction in GA growth is consistent with the natural history of the disease,” Dhaval Desai, PharmD, chief development officer of Iveric Bio, said in a news release.

EYP-1901 Shows Promise as Durable Anti-VEGF Treatment

■ Eyepoint Pharmaceuticals announced updated interim 8-month data from the DAVIO phase 1 clinical trial of EYP-1901, a bioerodible sustained delivery intravitreal anti-VEGF treatment targeting wet AMD. The data from phase 1 DAVIO, which enrolled 17 patients with previously treated wet AMD, confirm stable BCVA (-3.0 ETDRS letters), stable central subfield thickness (CST) on OCT (+13 μm), and a clinically significant 75% reduction in treatment burden. The interim data also continue to show no reports of ocular serious adverse events (SAEs) or drug-related systemic SAEs. There have been no reported events of vitreous floaters, endophthalmitis, retinal detachment, implant migration in the anterior chamber, retinal vasculitis, or posterior-segment inflammation. These data also revealed that 41% of eyes did not require any supplemental anti-VEGF injections up to 9 months following a single dose of EYP-1901.

“The DAVIO clinical trial update further reinforces the potential for EYP-1901 as a durable anti-VEGF treatment in wet AMD, and we look forward to initiating a phase 2 trial of EYP-1901 in the third quarter of 2022,” Jay S. Duker, MD, Chief Operating Officer of EyePoint Pharmaceuticals, said in a news release.

Kodiak’s ARMD Treatment Fails to Meet Primary Endpoints

■ Kodiak announced top-line results from its phase 2b/3 clinical trial of KSI-301, a novel antibody biopolymer conjugate, in treatment-naïve subjects with wet AMD. The results show that, although KSI-301 demonstrated strong durability and was safe and well tolerated, it did not meet the primary efficacy endpoint of showing noninferior visual acuity gains for subjects dosed on extended regimens compared to aflibercept given every 8 weeks.

The trial, which randomized 559 participants, had 2 treatment arms: KSI-301 5 mg on a flexible long-interval regimen and aflibercept 2 mg on a fixed short-interval regimen. In the study, 3 monthly loading doses were administered to all subjects at 0, 4, and 8 weeks. Subjects on aflibercept were then treated at fixed 2-month intervals. Subjects on KSI-301 were assessed starting 3 months after the completion of the loading phase (beginning at 20 weeks) and, based on predefined disease activity criteria, were treated every 3, 4, or 5 months.

“Allowing treatment with KSI-301 no more often than every 12 weeks after the loading phase for every patient turned out to be insufficient. Nonetheless, we believe the results demonstrate a clear anti-VEGF effect, strong durability, and a reassuring safety profile,” said Victor Perlroth, MD, Kodiak’s chief executive officer, in a news release.

KINGFISHER Study Meets Primary Objective of Noninferiority

■ Novartis announced that the KINGFISHER study, comparing brolucizumab 6 mg and aflibercept 2 mg, in patients with visual impairment due to DME, met its primary objective of noninferiority in change from baseline in BCVA at week 52. The two-arm, randomized, double-masked, multicenter phase 3 study included 495 patients who were randomly assigned 2:1 to receive monthly injections of either brolucizumab 6 mg or aflibercept 2 mg.

Noteworthy outcomes of the KINGFISHER study include superior anatomic improvements in terms of central subfield thickness, absence of intraretinal fluid (IRF), and subretinal fibrosis. Time to absence of retinal fluid was faster in the brolucizumab 6 mg arm. The incidence of intraocular inflammation, retinal vasculitis, and retinal vascular occlusion for brolucizumab vs aflibercept was 4.0% vs 2.9%, 0.9% vs 0.6%, and 0.3% vs 0.6%, respectively. Analysis of the study results revealed brolucizumab was superior to aflibercept in change from baseline in central subfield thickness at week 52, and at that time point a higher proportion of brolucizumab patients had normal central subfield thickness (<280 μm) than aflibercept patients. A higher proportion of brolucizumab compared with aflibercept patients had a fluid-free macula through week 52.

DORC International Launches Eva Nexus

■ DORC International launched Eva Nexus, a device aimed at improving efficiency and control in retina, cataract, and combined surgery. The platform introduces several innovations, including SmartIOP, a highly responsive infusion system for cataract surgery, enabling surgeons to work at lower infusion pressures and sustain a stable anterior chamber, even in challenging cases. The first randomized controlled trial of 250 cases with Eva Nexus was scheduled for completion in March. Eva Nexus is available now in CE-marked countries; 510k clearance for the United States is expected later in 2022. During a limited release of the device, surgeons have performed more than 1,500 cataract surgeries and 400 vitrectomies at 5 surgical centers.

New Data Show Favorable Tolerability for OTX-TKI for Wet AMD

■ Ocular Therapeutix released new data from its phase 1 trial of OTX-TKI (axitinib intravitreal implant) for the treatment of neovascular AMD, including that approximately 50% of all subjects showed implant durability of 7.5 months or longer. The update was delivered by Andrew A. Moshfeghi, MD, of University of Southern California Roski Eye Institute, at the virtual 2022 Angiogenesis, Exudation, and Degeneration Symposium. He reported that OTX-TKI has been generally well tolerated and observed to have a favorable safety profile, in treatment-naive and previously treated wet AMD patients, and no ocular serious events or measurable systemic exposure to axitinib, a small molecule multireceptor tyrosine kinase inhibitor, was observed in cohorts 1 (200 μg), 2 (400 μg), 3a (600 μg); or 3b (400 μg + anti-VEGF).

A preliminary biologic signal of a clinically meaningful decrease in retinal fluid was observed by the 2-month mark in cohorts 2 and 3a, and as early as 1 week in cohort 3b. More than 60% of subjects showed durability of the implant for 6 months or longer, including more than 80% in cohort 3a. There was a preliminary biological signal of clinically meaningful decrease in retinal fluid, with some subjects in cohorts 2 and 3a showing a decrease in intraretinal or subretinal fluid by 2 months.

Regeneron Reveals Encouraging Phase 2 Results for High-dose Aflibercept

■ Regeneron Pharmaceuticals announced new results from its phase 2 trial evaluating an investigational 8 mg dose of aflibercept compared to the currently approved 2 mg dose of Eylea (aflibercept) in patients with wet AMD. The newest outcomes show that aflibercept 8 mg continues to show numeric improvements in anatomic and vision outcomes compared to Eylea through 44 weeks.

Eyes treated with aflibercept 8 mg were more likely to be dry in the center subfield on OCT compared to Eylea at every timepoint measured throughout the trial, after the initial monthly dosing period. At week 44, when the trial ended: 40% of patients treated with aflibercept 8 mg did not have fluid in the center subfield compared to 28% of patients treated with Eylea; twice as many patients treated with aflibercept had no macular fluid compared to patients treated with Eylea; 7.9 average letter improvement from baseline in the aflibercept group compared to 5.1 letters in the Eylea group; and almost half (47%) of aflibercept patients achieved at least a 10-letter gain and more than a quarter (28%) achieved more than 15 letters, compared to 35% and 18% for patients treated with Eylea, respectively.

Oxurion Releases Newest KALAHARI THR-149 for DME Data

■ Oxurion released the newest data from KALAHARI, a clinical trial assessing THR-149, for treatment of DME patients showing suboptimal response to anti-VEGF therapy. Post-hoc analysis revealed a >9 letter gain in mean BCVA that was maintained for the remaining 4 months of the trial after the last THR-149 injection, with no rescue treatment required. These outcomes stem from analysis of a masked OCT biomarker assessment that identified 2 subjects with abnormalities at baseline. Excluding these subjects resulted in an improvement in mean BCVA of 9.3 letters at month 3 that was sustained until month 6, the end of the trial. The data also demonstrated THR-149’s attractive safety profile and its ability to stabilize CST.

Arshad M. Khanani, MD, MA, director of clinical research at Sierra Eye Associates, Reno, Nevada, said in a news release, “For patients who are suboptimal responders to standard-of-care anti-VEGF therapy, the post-hoc analysis of the high-dose cohort in the KALAHARI trial showed encouraging gains in BCVA with over 80% of patients gaining at least 5 letters and 50% of patients gaining at least 10 letters 4 months after the last THR-149 injection. These results demonstrate the potential of THR-149 to make a meaningful difference to this patient population.”

Some Wet AMD Patients May Eventually Safely Stop Injections

■ In a preliminary study of 106 people with wet AMD, Johns Hopkins Medicine researchers found that as many as a third of patients may someday be able to safely stop eye injection therapy without further vision loss. The findings did not identify a timeline for ending treatment or predict which patients can stop injections, but the results support evidence that many people with the disease may not need lifelong injections. The findings point to proteins produced at different levels in the eyes of those who stopped therapy, which may lead to development of a test to accurately identify who may be weaned off medication.

Ocuphire Pharma Completes Enrollment in ZETA-1 Trial

■ Ocuphire Pharma announced that it has completed enrollment of 103 diabetic patients, with moderately severe to severe nonproliferative diabetic retinopathy (NPDR) or mild PDR, in ZETA-1. This phase 2b trial is evaluating the efficacy and safety of APX3330 for the treatment of diabetic retinopathy at 25 investigational sites across the United States. In the study, subjects are randomized to receive 600 mg APX3300 or placebo daily over 24 weeks. The primary endpoint is the percentage of subjects with a ≥2 step improvement on the Diabetic Retinopathy Severity Scale. Secondary endpoints include evaluation of central subfield thickness, BCVA, safety, and tolerability.

FDA Clears AffaMed Therapeutics’ Treatment IND

■ AffaMed Therapeutics announced that the FDA has cleared its Investigational New Drug (IND) application for the clinical development of AM712 (ASKG712), a novel proprietary bispecific biologic molecule blocking both VEGF and angiopoietin-2 (Ang-2), for the treatment of retinal vascular diseases. Under this IND, AffaMed will initiate a phase 1 study in the United States to investigate the safety, tolerability, pharmacokinetics, and efficacy of AM712 in subjects with neovascular AMD.

In preclinical studies, AM712 demonstrated robust efficacy, adequate ocular pharmacokinetics, and the desired safety profile supporting clinical exploration. AffaMed Therapeutics recently entered into a licensing agreement with AskGene Pharma Inc. for the exclusive rights to develop, manufacture, and commercialize AM712 in ex-Asia and Japan territories globally.

PALADIN Study With ILUVIEN Published in Ophthalmology

■ Alimera Sciences announced that the 3-year results of the PALADIN study have been published in the peer-reviewed journal Ophthalmology. The PALADIN study was designed and developed to confirm the benefit of using a prior course of corticosteroid as indicated in the ILUVIEN US label, to mitigate the risk of uncontrolled IOP elevation.

The study results show that patients with DME who received a single dose of the sustained-release implant ILUVIEN (fluocinolone acetonide intravitreal implant) 0.19 mg demonstrated statistically significant improvements in BCVA, CST, and treatment burden at 36 months. Treatment frequency for PALADIN subjects was reduced from a median of 3.4 treatments per year in the 36 months preceding the ILUVIEN injection to a median of 1.0 treatments per year in the 36 months following the ILUVIEN injection.

Ocuphire Appoints Chief Medical Advisor

■ Ocuphire Pharma, Inc., a clinical-stage ophthalmic biopharmaceutical company focused on developing and commercializing therapies for the treatment of refractive and retinal eye disorders, announced the appointment of Jay Pepose, MD, PhD, as its chief medical advisor.

“We are thrilled to name Dr. Pepose as our chief medical advisor,” said Mina Sooch, MBA, founder and CEO of Ocuphire Pharma, in a news release. “We are delighted that he will deepen his engagement with our operational and leadership teams at Ocuphire. Dr. Pepose’s appointment also comes at a strategic time for our company, as we look forward to important clinical and regulatory milestones, including a phase 2 APX3330 readout for diabetic retinopathy in the second half of 2022, the initiation of the presbyopia phase 3 program for both Nyxol and Nyxol with low-dose pilocarpine, and a potential NDA submission for Nyxol in reversal of mydriasis in late 2022.”

Eyebio Raises Series A Funding for New Eye Disease Therapies

■ Eyebio, which launched in 2021 with a mission to protect, restore, and improve vision for people who are underserved by available eye disease therapies, announced the completion of a successful $65 million Series A funding round. SV Health Investors led the round, alongside Samsara BioCapital and Jeito Capital, with additional financial backing from MRL Ventures. The company will use proceeds from the Series A to develop a diversified pipeline of product candidates. EyeBio was founded by David Guyer, MD, and Anthony P. Adamis, MD, in collaboration with SV Health Investors. Previously, Dr. Guyer and Dr. Adamis collaborated with SV Health Investors to co-found Eyetech Pharmaceuticals, where they developed and commercialized the first anti-VEGF drug for the treatment of AMD.

Kiora Granted Orphan Drug Designation for Investigational RP Drug

■ Kiora Pharmaceuticals has received Orphan Drug Designation from the FDA for KIO-301, its investigational treatment of retinitis pigmentosa (RP). Kiora plans to begin a phase 1b clinical trial in Australia later this year before initiating larger studies in the United States and worldwide, according to Brian M. Strem, PhD, president and CEO of Kiora.

“While RP can be caused by a variety of gene mutations, our small-molecule KIO-301 has the potential to be used as a standalone therapy regardless of the underlying mutations or in combination with next-generation gene-specific therapies,” Dr. Strem said in a news release.

Kriya Licenses Next-generation Gene Therapies

■ Kriya announced an exclusive agreement with the Medical University of South Carolina (MUSC) Foundation for Research Development to license next-generation complement-targeted gene therapies for the treatment of GA and other ocular diseases.

“Recent advances in complement inhibitor therapies have provided important additional evidence that targeting complement holds great promise in treating GA. By targeting the inhibition of complement proteins directly involved in complement activation, our approach has the potential to deliver a selective and profound biological effect,” Bärbel Rohrer, PhD, professor of ophthalmology at the Medical University of South Carolina and coinventor of the technology, said in a news release.

MeiraGTx Receives Development Milestone Payment for XLRP Trial

■ MeiraGTx announced that it has received $30 million from Janssen Pharmaceuticals, Inc., part of Johnson & Johnson, for a clinical milestone in the phase 3 Lumeos trial of botaretigene sparoparvovec, (formerly called AAV-RPGR), an investigational gene therapy for the treatment of X-linked retinitis pigmentosa (XLRP). MeiraGTx and Janssen are jointly developing botaretigene sparoparvovec as part of a broader collaboration to develop and commercialize gene therapies for the treatment of inherited retinal diseases. Botaretigene sparoparvovec, which has been granted fast track and orphan drug designations by the FDA, is designed to deliver functional copies of the RPGR gene to the retina to improve and preserve vision.

Prima System Study Published in Nature Communications

■ Pixium Vision announced that a paper outlining data from its ongoing Prima System PRIMAvera study for the treatment of atrophic dry AMD, has been published in Nature Communications. “The publication of these data in this prestigious journal demonstrates the validation by our peers of the highly innovative and promising nature of our Prima System. The data highlighted in this publication support that patients can combine their remaining peripheral vision with our bionic vision, that the resolution of perception is close to the resolution of the implant, and that natural peripheral vision is not reduced over time following the implantation,” said Lloyd Diamond, CEO of Pixium Vision, in a news release.

Regenerative Patch Shows Promise in Patients With Advanced AMD

■ Regenerative Patch Technologies announced that results from its phase 1/2a clinical trial of the CPCB-RPE1 implant for advanced dry AMD have been published online in Stem Cell Reports. The publication describes immunologic and histologic results from the clinical trial. Subjects in the trial were all legally blind in the treated eye at enrollment and the implants were delivered to large areas of degenerative disease stemming from GA. At an average of 34 months post-implantation, 27% of patients (4 of 15) showed >7 letter improvement in BCVA, which ranged from 7-15 letters or 1 to 3 lines on an eye chart; 33% (5/15) remained stable with a BCVA within 5 letters of baseline value.

Rezolute Releases Top-line Data From Oral DME Study

■ Rezolute announced top-line data from its phase 1b multiple-ascending dose (MAD) study of RZ402, a plasma kallikrein inhibitor (PKI) being developed as an oral therapy for the treatment of DME. Results of the MAD study support the potential for once-daily oral dosing and enable the company to initiate a phase 2 proof-of-concept study later this year. The MAD study showed dose-dependent increases in systemic exposures, with repeat-dosing to steady-state resulting in the highest concentrations of RZ402 explored to date. “RZ402 has the potential to substantially alter the DME treatment paradigm by providing a less invasive alternative for patients,” Raj Agrawal, MD, vice president of Rezolute, said in a news release. RP