Apellis Responds to ReST Notice Regarding Syfovre IOI Complications

■ Several cases of intraocular inflammation (IOI) following the administration of Apellis Pharmaceuticals’ drug Syfovre (pegcetacoplan injection) have been reported by physicians, according to a statement issued by the ASRS Research and Safety in Therapeutics (ReST) Committee to its members in late July. After a thorough review, Apellis released a statement explaining that there is no indication that drug product or manufacturing issues contributed to the IOI. The Apellis statement said, “No manufacturing related issues impacting product quality were identified, no quality issues and no contaminants (eg, endotoxins) were discovered, no single manufacturing lot was implicated, no indication of drug related immunogenicity was observed in the clinical trial data, zero events of retinal vasculitis were reported by investigators or identified by an independent reading center in the phase 3 clinical trials.” In addition, Apellis re-reviewed the reported IOI cases and reported that there were no vasculitis events, and external retina/uveitis specialists re-reviewed all severe IOI cases and further confirmed no vasculitis events.

“Following 68,000 commercial vials distributed and 23,000 clinical trial injections to date, these [IOI] events continue to be very rare. Additionally, as part of our ongoing review, we have seen no indication that drug product or manufacturing issues contributed to these events,” Cedric Francois, MD, PhD, cofounder and CEO of Apellis, said in a news release.

Ocular Therapeutix Announces OTX-TKI Study Updates

■ Ocular Therapeutix announced updates in the study of its axitinib intravitreal hydrogel implant OTX-TKI for wet age-related macular degeneration (AMD) and diabetic retinopathy (DR). The company reported that 12-month data from its phase 1 US clinical trial evaluating OTX-TKI for wet AMD demonstrated maintenance of controlled wet AMD subjects comparable to aflibercept injections every 8 weeks with a single administration of OTX-TKI. Four subjects received rescue therapy for the first time at month 12.

“Pharmacodynamic effects observed in this trial support the characteristics of a treatment for wet AMD with durability between 9 to 12 months with a single injection. Following discussions with the FDA, we have 2 potential pivotal designs and are prepared to initiate a first pivotal trial for OTX-TKI in wet AMD as early as the third quarter of this year,” Antony Mattessich, president and CEO of Ocular Therapeutix, said in a news release.

The company also recently completed enrollment of the phase 1 HELIOS clinical trial to evaluate OTX-TKI for the treatment of DR, and 6-month interim results are expected in the first quarter of 2024.

Positive Findings Reported From Oculis DME Eye Drop Study

■ Oculis announced positive top-line results from stage 1 of its phase 3 DIAMOND trial of OCS-01 eye drops in diabetic macular edema (DME). Stage 1 was conducted in 39 sites across the United States and Europe with 148 patients randomized 2:1 to receive OCS-01 or vehicle 6 times daily for a 6-week loading phase and then 3 times daily for a subsequent 6-week maintenance phase. In this 3-month trial, OCS-01 met both clinical efficacy endpoints: main BCVA change and proportion of patients with 3 lines of vision gain. An effect on retinal thickness was also observed with a statistically significant decrease in central subfield thickness at week 6 vs baseline in the OCS-01 treatment arm. The decrease in retinal thickness persisted to week 12.

“OCS-01 has been validated in 2 different studies with consistent and repeated positive results. We remain focused on advancing with high priority the DIAMOND phase 3 trial to stage 2. This important milestone has the potential to bring us one step closer to providing the first treatment in the form of eye drops to patients with DME,” Riad Sherif, MD, CEO of Oculis, said in a news release.

Adverum Grants License to Ray Therapeutics for Intravitreal Capsid

■ Adverum Biotechnology announced that the company has granted a nonexclusive, royalty-bearing license to Ray Therapeutics for the use of Adverum’s intravitreal delivery platform, AAV.7m8, to be used in conjunction with Ray Therapeutics gene therapy product, RTx-015.

“Visual optogenetics is a disruptive technology that affords the opportunity to restore life-transforming levels of vision to blind and visually impaired patients with conditions such as retinitis pigmentosa,” Paul Bresge, CEO of Ray Therapeutics, said in a news release. “We have developed a next-generation bioengineered optogenetic payload which we believe is optimized for human vision. When delivered using previously studied low doses of AAV.7m8, we anticipate levels of target retinal ganglion cell transduction that could realize the full potential of our RTx-015 asset.”

AiViva Initiates Phase 1 Clinical Trial of AIV007 for AMD and DME

■ AiViva Biopharma announced that it has begun a phase 1 trial of AIV007, a broad-spectrum tyrosine kinase inhibitor, targeting the convergence of fibrosis, angiogenesis, and inflammation; and has completed dosing the first cohort of patients diagnosed with wet age-related macular degeneration (AMD), and/or diabetic macular edema (DME). This is a multicenter, open-label, dose-escalation safety clinical trial. Up to 24 subjects will receive a single periocular injection and will undergo monthly evaluation for up to 6 months. “We believe AIV007 coupled with our proprietary JEL technology for periocular administration will address the root causes of many ocular diseases,” Diane Tang-Liu, PhD, CEO, president and cofounder of AiViva, said in a news release.

Alimera Completes Recruitment for Landmark NEW DAY Study

■ Alimera Sciences announced that it has completed enrollment for the company’s NEW DAY clinical trial, a randomized, controlled, multicenter study designed to generate prospective data for Iluvien (fluocinolone acetonide intravitreal implant) 0.19 mg as a baseline therapy in patients diagnosed with diabetic macular edema (DME). The NEW DAY study currently has enrolled approximately 300 treatment-naïve, or near naïve, DME patients in approximately 42 sites in the United States.

Patients are randomized to receive either 5 injections of intravitreal aflibercept 2 mg at 4-week intervals for the first 16 weeks or an Iluvien intravitreal implant. The primary outcome measure is the mean number of supplemental injections needed during the trial between treatment groups.

“We look forward to sharing data in early 2025, which we expect will support a change to the current paradigm of DME treatment,” Rick Eiswirth, Alimera’s president and CEO, said in a news release.

FDA Issues Complete Response Letter, Declines to Approve Aflibercept 8 mg

■ Regeneron announced that it has received a complete response letter (CRL) from the FDA following the company’s Biologics License Application (BLA) for aflibercept 8 mg for the treatment of patients with wet age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy (DR). A CRL indicates that the review cycle for an application is complete, but that the FDA deems the application not ready for approval. In a news release, the company noted that no additional clinical data or trials have been requested, and that the CRL was due to an ongoing review of inspection findings at a third-party filler. Additionally, the statement explained that the CRL did not identify any issues with the drug’s safety or efficacy, with the trial design or labeling, or with drug manufacturing.

In related news, positive 2-year results from the pivotal PHOTON trial investigating aflibercept 8 mg with 12-week and 16-week dosing regimens, compared to Eylea injection, in patients with DME were presented at the American Society of Retina Specialists Annual Scientific meeting. Among the results: 89% maintained ≥12-week dosing intervals through 2 years, and 83% maintained ≥16-week dosing intervals through 2 years.

“Maintaining 2 years of vision and anatomic improvements with as few as 3 or 4 injections per year, while not compromising safety, is impressive and could make a meaningful difference in the lives of the patients we treat,” Diana V. Do, MD, professor of ophthalmology and vice chair for clinical affairs at the Byers Eye Institute of Stanford University and a trial investigator, said in a news release.

Annexon Presents ARCHER Trial Results at Annual ASRS Meeting

■ Annexon announced that results from the ongoing phase 2 ARCHER trial of intravitreal ANX007 in patients with geographic atrophy (GA) were presented at the American Society of Retina Specialists Annual Scientific meeting. ANX007 is an investigational, humanized antibody antigen-binding fragment that inhibits C1q and has a neuroprotective mechanism of action. The primary biomarker endpoint was change in GA lesion area assessed by autofluorescence at 12 months.

Results presented by ARCHER investigator Jeffrey S. Heier, MD, director of the retina service and retina research at Ophthalmic Consultants of Boston, included that ANX007 demonstrated visual function benefits that were dose dependent and time dependent and that GA lesion growth was slowed in both treatment arms. The company has plans for regulatory discussions with the FDA to move to phase 3 study.

Aviceda Doses First Patient With Nanoparticle in Phase 2 GA SIGLEC Trial

■ Aviceda announced the dosing of the first patient with AVD-104 in its phase 2 SIGLEC trial. This lead intravitreal asset used for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a novel glycan-coated nanoparticle supported by a strong preclinical in vivo efficacy and safety profile.

“AVD-104 attacks 2 fundamental processes in GA by modulating critical inflammatory pathways through the inhibition of retinal macrophage inflammatory activity and repolarization of activated macrophages to their resolution states, and, through inhibition of complement cascade amplification. We have designed our phase 2 trial to move efficiently through dose escalation and to increase the chances of seeing early signals of clinical activity,” David Callanan, MD, chief medical officer of Aviceda, said in a news release.

Bausch + Lomb Launches PreserVision AREDS 2 Formula in United States

■ Bausch + Lomb announced the US launch of PreserVision AREDS 2 Formula soft gels plus coenzyme Q10 (CoQ10). PreserVision AREDS 2 Formula eye vitamins plus CoQ10 combines the nutrient formula recommended by the National Eye Institute, to help reduce the risk of moderate-to-advanced age-related macular degeneration (AMD) progression, with CoQ10, to help support heart health.”

We developed this two-in-one formula to help make it easier for patients with AMD to support both their eye and heart health,” John Ferris, an executive vice president with Bausch + Lomb, said in a news release.

Analysis Shows Tepid Acceptance of Ranibizumab Biosimilars

■ Uptake and user base of biosimilars Byooviz (Biogen) and Cimerli (Coherus) have both been low, and general attitudes around biosimilars seem to be cooling, according to a recent analysis from Spherix Global Insights. Spherix has been tracking ophthalmologists’ attitudes and perceptions around biosimilars in its Special Topix: Ophthalmology Biosimilars Today and Tomorrow (US) series since Q4 2021 in anticipation of the launch of Byooviz and Cimerli last year. The candidacy pool of potential Byooviz and Cimerli patients is thought to be substantial, yet most ophthalmologists surveyed have yet to prescribe either medication. Furthermore, many have no plans to try the agents, citing a lack of comfort and familiarity, along with excessive costs and poor formulary status.

UBX1325 Fails to Meet Noninferiority Endpoint Despite Good Wet AMD Results

■ Unity BioScience reported that UBX1325, a Bcl-xL inhibitor, did not achieve noninferiority to aflibercept, despite good 6-month results, in the part A portion of ENVISION, a phase 2 wet age-related macular degeneration (AMD) trial. The trial involved 51 patients with wet AMD who received either two 10-μg doses of UBX1325 at week 0 and week 4 or aflibercept 2 mg every 8 weeks. More than half of the patients on UBX1325 avoided anti-VEGF treatment for at least 6 months.

UBX1325 was generally well tolerated with no intraocular inflammation, and visual acuity remained stable through 24 weeks in patients with active disease. However, there was a 3.5 letter gain in the aflibercept arm at 2 weeks, whereas for patients on UBX1325 monotherapy, visual acuity decreased by 0.8 letters from baseline. According to the company, based on post hoc assessments, UBX1325 may have greater treatment effect in patients with AMD diagnosis greater than 2 years.

Clearside Opens Enrollment in ODYSSEY Phase 2b Trial of CLS-AX

■ Clearside Biomedical announced that enrollment has opened in ODYSSEY, its phase 2b clinical trial of the tyrosine kinase inhibitor CLS-AX (axitinib injectable suspension) in neovascular age-related macular degeneration. ODYSSEY is a randomized, double-masked, parallel-group, active-controlled, multicenter, 36-week trial comprising 60 total participants with 2:1 randomization, with 40 participants in the CLS-AX arm and 20 participants in the aflibercept (Eylea; Regeneron) arm.

“We are targeting a total of 30 US-based clinical trial sites for ODYSSEY and expect to report top-line data from the trial in the third quarter of next year,” George Lasezkay, PharmD, JD, Clearside’s president and CEO, said in a news release.

Formycon and Klinge Submit Biologics License Application for FYB203

■ Formycon and its license partner Klinge Biopharma announced that their biologics license application (BLA) for FYB203, a biosimilar candidate for the anti-VEGF drug Eylea (aflibercept; Regeneron) has been submitted to the FDA.

“FYB203 is an excellent complement to our ophthalmic portfolio and in addition to our already approved ranibizumab biosimilar (FYB201), we are fully committed to making another highly effective treatment option available,” Formycon chief scientific officer Andreas Seidl said in a news release.

Newly Released Vabysmo Data Presented at Annual ASRS Meeting

■ Genentech announced that new 2-year data show that Vabysmo (faricimab-svoa) maintains its effectiveness 4 months after injection in patients with wet age-related macular degeneration and diabetic macular edema (DME). The data, which were presented at the American Society of Retina Specialists Annual Scientific meeting, indicate that more than 60% of Vabysmo patients could be treated every 4 months. Also, 2-year post hoc data on epiretinal membrane formation in DME patients that indicated that Vabysmo leads to less retinal fibrosis than aflibercept were presented for the first time.

“The clinical and real-world data at ASRS reinforce the improvement in outcomes brought by Vabysmo in 2 leading causes of vision loss, particularly new analyses suggesting that Vabysmo is associated with less vision-impacting fibrosis than aflibercept,” Levi Garraway, MD, PhD, Genentech chief medical officer and head of global product development, said in a news release.

iHealthScreen Submits 510(k) Application for Artificial Intelligence AMD Diagnosis Tool

■ iHealthScreen announced that it has submitted an application to the FDA for 510(k) clearance for iPredict, an automated AI-based screening software for early diagnosis of age-related macular degeneration (AMD). The company conducted a prospective trial in the general population to assess the product’s accuracy, sensitivity, and specificity, and found that the device demonstrated accuracy with a sensitivity of 86.86% and a specificity of 94.13%.

“This technology could be particularly useful in identifying someone who has slipped across the boundary for progression into severe AMD,” Theodore Smith, MD, professor of ophthalmology and neuroscience at Icahn School of Medicine at Mount Sinai, New York, said in a news release.

Coave Announces Positive Data From RP Gene Therapy Trial

■ Coave announced positive 12-month results from its phase 1/2 trial evaluating the safety and efficacy of CTx-PDE6b, a gene therapy for retinitis pigmentosa (RP) caused by biallelic mutations in the PDE6b gene (PDE6b RP). To date, CTx-PDE6b has been administered to 17 patients aged 18 years and older presenting with an advanced form of PDE6b RP using 2 ascending doses, and both doses were well tolerated (n=17).

A subgroup of patients (n=6) with less advanced disease who received the higher dose showed positive efficacy results across all 5 clinical endpoints (BCVA, visual field, microperimetry, full-field sensitivity test, and mobility test), as well as optical coherence tomography. In addition, Coave has received regulatory approval to expand the ongoing trial to include a new cohort of 6 younger patients (aged 13 to 25 years) with earlier stages of disease.

Cognition Doses First Patient in MAGNIFY Study of Oral CT1812 for GA

■ Cognition Therapeutics announced that it has dosed the first participant in the phase 2 MAGNIFY study of CT1812, an experimental oral therapy being developed for the treatment of geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). The MAGNIFY study is a randomized, placebo-controlled trial that is expected to enroll approximately 246 adults who have been diagnosed with dry AMD with measurable GA. CT1812 will be given once daily for 24 months to determine if it can slow disease progression. CT1812 is a small-molecule sigma-2 receptor modulator.

FDA Grants Orphan Drug Status to Combo Stain for ILM and ERM

■ DORC announced that it has received notification from the FDA that the company’s application for orphan drug designation has been granted for a combination of Trypan Blue and Brilliant Blue G (BBG) ophthalmic solutions.

The proposed indication for the combination of 0.15% Trypan Blue and 0.025% BBG is to selectively stain the epiretinal membrane (ERM) and internal limiting membrane (ILM). Orphan-drug designation promotes the development of new therapies for rare diseases and disorders affecting fewer than 200,000 individuals in the United States.

Comprehensive AI-driven Real-world Ophthalmology Database in the Works

■ RetinAI Medical and Retina Consultants of America (RCA) announced a strategic partnership to develop the most extensive real-world evidence US-based database in ophthalmology, driven by artificial intelligence (AI) insights into real-world evidence. RetinAI is a leader in clinical and imaging data management software and advanced analytics using AI, and RCA is the largest retina care provider in the United States, with more than 1.7M annual patient visits and more than 200 locations.

The partnership will leverage RetinAI’s digital health technologies and RCA’s network of clinics to analyze real-world health data. The aim is to amass a comprehensive resource that provides valuable insights into health outcomes, medication adherence, and the effectiveness of treatment protocols.

First Patients Dosed in EyeBio’s Phase 1b/2 Restoret Trial

■ EyeBio announced the dosing of the first participants in its phase 1b/2 AMARONE (Anti-permeability Mechanism and Age-Related Ocular Neovascularization Evaluation) clinical trial in patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (AMD). The AMARONE trial will evaluate the safety and preliminary efficacy of intravitreal Restoret (EYE103) and is the first clinical trial of EyeBio’s multispecific antibodies. Restoret is an investigational, intravitreally delivered, trispecific antibody designed to resolve residual fluid in the retina and to improve visual acuity in individuals with wet AMD and DME, as well as other retinal diseases of permeability.

EyeCare Partners Introduces Comprehensive Ophthalmology Fellowship

■ EyeCare Partners announce the launch of its new Advanced Comprehensive Ophthalmology Fellowship (ACOF), a 1-year program designed to provide training to residency graduates in the latest advancements in ophthalmology. ACOF was developed by the EyeCare Partners Innovation Center, which was launched last fall to advance eye care quality, research, and education. The fellowship program, which starts in the fall of 2024, will be sponsored by John Sheppard, MD, founder of Virginia Eye Consultants; Edward Meier, MD, Cincinnati Eye Institute; and Timothy Page, MD, Oakland Ophthalmic Surgery. RP

EyePoint Completes Enrollment in Phase 2 Trial of EYP-1901

EyePoint has announced that the company has completed enrollment in the PAVIA clinical trial evaluating EYP-1901 as a potential 9-month treatment for moderate-to-severe nonproliferative diabetic retinopathy. The 12-month, randomized, controlled phase 2 clinical trial has enrolled 77 patients randomly assigned to 1 of 2 doses of EYP-1901 (approximately 2 mg or 3 mg), or to the control group receiving a sham injection. The primary efficacy endpoint of the trial is improvement of at least 2 diabetic retinopathy severity scale levels as of week 36 after the EYP-1901 injection.

“We are particularly pleased to have enrolled 77 patients in this trial, exceeding the 60-patient target,” Nancy Lurker, CEO of EyePoint Pharmaceuticals, said in a news release.

Noninvasive Approach Predicts Retinopathy of Prematurity Earlier

Researchers at Ann & Robert H. Lurie Children’s Hospital of Chicago have found that imaging the capillaries in the nailbed of premature infants within the first month of life using a noninvasive technique called nailbed capillaroscopy can identify infants at high risk for developing retinopathy of prematurity. A cohort of 32 premature neonates were studied.

“Earlier identification of these infants reduces the need to subject all premature babies to highly invasive eye exams,” said lead study author and neonatologist Isabelle De Plaen, MD, in a news release.

OcuTerra Completes Enrollment in Phase 2 of DR:EAM Study

OcuTerra announced full enrollment in the company’s phase 2 DR:EAM (Diabetic Retinopathy: Early Active Management) clinical trial evaluating topically delivered OTT166 eye drops in adults with moderately severe to severe nonproliferative diabetic retinopathy or mild proliferative diabetic retinopathy with minimal vision loss. The DR:EAM study is a multicenter, randomized, double-masked clinical trial designed to assess the safety and efficacy of a high and low dose of daily topical OTT166 vs vehicle. The trial enrolled 225 patients who were randomly assigned 1 of 2 doses of OTT166 or to 1 of 2 control groups receiving vehicle.

Optos Announces New Ultrawidefield Color Image Modality

Optos announced that it is expanding the Optomap ultrawidefield (UWF) retinal imaging modalities of its California FA device. In addition to Optomap color rg (red/green), sensory red-free, choroidal, autofluorescence (AF), fluorescein angiography (FAF), and indocyanine green angiography (ICGA) modalities, the company will debut the first ultrawidefield color rgb (red/green/blue) image. In a news release, David M. Brown, MD, Retina Consultants of Texas, said, “The Optomap color rgb is particularly impressive in its ability to discern holes in peripheral lattice degeneration and retinoschisis.”

Intravitreal R100 Vector to Be Used for Rare Ophthalmic Targets

Astellas Pharma and 4D Molecular Therapeutics (4DMT) announced a license agreement under which Astellas gains rights to utilize the intravitreal retinotropic R100 vector invented by 4DMT for 1 genetic target implicated in rare monogenic ophthalmic diseases, with options to add up to 2 additional targets implicated in rare monogenic ophthalmic diseases after paying additional option exercise fees.

In related news, 4DMT announced that it has completed enrollment of the phase 2 dose expansion stage of the PRISM clinical trial of 4D-150 for patients with wet age-related macular degeneration over approximately 2 quarters, and that no significant 4D-150 safety events or inflammation had been reported at press time.