RetinAI’s Data Management Platform Gets FDA Clearance

■ RetinAI Medical announced that its ophthalmology image and data management platform, Discovery, has been granted 510k clearance from the FDA. The Discovery platform can be used to organize and analyze images, such as OCT scans and fundus photographs. It provides secure, web-based access to facilitate interactive analysis of clinical cases in real time. Features such as multimodal imaging, comparison views of clinical visits, deployment of grading surveys, and electronic case report forms for collecting clinical data are all integrated into the platform. In a news release, RetinAI’s CEO, Carlos Ciller, PhD, said, “We’ve already seen the benefits of how Discovery streamlines management and analysis in clinical studies and clinics in Europe, and we are excited to bring our innovation to the US.”

Clearside Presents Suprachoroidal Injection Update

■ Several posters about Clearside Biomedical’s suprachoroidal delivery platform, Xipere, and gene therapy delivery using Clearside Medical’s SCS Microinjector, were presented at ARVO 2022. “Our data presented at ARVO demonstrated that suprachoroidal delivery via our SCS Microinjector enabled targeting, compartmentalization, and durability of small molecule suspensions, thereby potentially addressing some of the efficacy, safety, and treatment burden limitations of current retinal therapies,” Thomas A. Ciulla, MD, MBA, chief medical officer and chief development officer at Clearside Biomedical, said in a news release.

One of the posters, entitled “Targeting, Compartmentalization and Durability of Suprachoroidally Injected Small Molecule,” summarized the preclinical and clinical evaluation of SCS Microinjector suprachoroidal delivery, and its synergy with small molecule suspensions. The poster confirmed posterior spread and opening of the SCS immediately after the suprachoroidal injection.

C. Light Technologies Raises Funds for Eye-tracking Technology

■ C. Light Technologies announced the closing of its $2.5 million seed round of funding for the development of neural network analytics technology to advance the development of a proprietary retinal eye-tracking device that uses high-resolution retinal videos to map eye motion, as well as to predict multiple sclerosis progression. The technology captures eye motion data with a sensitivity to 1 micron of movement. The new round brings the company’s total funding to date to more than $3.25 million, which includes more than $475,000 in grant funding from the National Institutes of Health.

AAO Commends Congress for Prior Authorization Reform Bill

■ The American Academy of Ophthalmology commended the US House of Representatives, in a news release, for surpassing the 290-cosponsor milestone in support of HR 3173, The Improving Seniors’ Timely Access to Care Act of 2021. The two-thirds majority of bipartisan support in Congress makes the bill eligible for inclusion on the Consensus Calendar under new rules established in 2019.

If enacted, this legislation would provide oversight and transparency while protecting beneficiaries from unnecessary care delays and denials. The legislation would require Medicare Advantage (MA) plans to establish an electronic prior authorization (ePA) program and require MA plans to adopt ePA capabilities, including the ability to provide real-time decisions; annually publish specified prior authorization information; ensure prior authorization requests are reviewed by qualified medical personnel; and protect beneficiaries from any disruptions in care due to prior authorization requirements as they transition between MA plans.

AGTC Reports Positive Interim Results From X-linked RP Trial

■ Applied Genetic TechnologiesCorporation (AGTC) reported positive 3-month interim data from its ongoing phase 2 Skyline trial of AGTC-501, a recombinant AAV viral vector-based gene therapy targeting mutations in the RPGR gene in patients with X-linked retinitis pigmentosa (XLRP). There were robust improvements in visual sensitivity, the trial’s primary efficacy endpoint, in multiple patients 3 months after dosing, with a 62.5% response rate in dose group B and a 25% response rate in dose group A. This is well above the 50% response rate the Vista phase 2/3 trial for XLRP is powered to detect.

“We are incredibly excited by the compelling interim results seen in the Skyline trial, including strong safety data and robust improvements in visual sensitivity with a clear difference between the 2 dose groups,” Sue Washer, president and CEO of AGTC, said in a news release.

Pegcetacoplan Continues to Show Reduced Growth of Lesions

■ Apellis Pharmaceuticals released longer-term data from the phase 3 DERBY and OAKS studies of intravitreal pegcetacoplan, an investigational, targeted C3 therapy, for the treatment of geographic atrophy (GA) secondary to AMD. Monthly and every-other-month pegcetacoplan showed a continuous and clinically meaningful reduction in the growth of both extrafoveal and foveal lesions at month 18. Roger Goldberg, MD, of Bay Area Retina Associates, presented the data at ARVO 2022. He reported that in the combined OAKS and DERBY studies, pegcetacoplan reduced extrafoveal GA lesion growth by 26% and 21% with both monthly and every-other-month treatment, respectively, and reduced foveal lesion growth by 13% and 13%, respectively.

“Slowing disease progression and preserving vision longer is critical for all patients with GA, so I am very encouraged that pegcetacoplan continuously reduced lesion growth over time in patients who are representative of the real-world GA population,” Dr. Goldberg said in a news release.

UK Grants License for Ophthalmology Biosimilar Ongavia

■ Teva Pharmaceutical announced that UK Medicines & Healthcare Regulatory Agency (MHRA) has granted a license for Ongavia, a biosimilar to Lucentis (ranibizumab). The United Kingdom is the first country in Europe to authorize commercialization of Ongavia for the treatment of wet AMD. Ongavia is also licensed for the treatment of diabetic macular edema, proliferative diabetic retinopathy, macular edema secondary to branch or central retinal vein occlusion, and choroidal neovascularization.

Teva’s biosimilar ranibizumab is similar to its reference medicine in terms of clinical efficacy as well as ocular and systemic safety in the treatment of patients with AMD and its other indications. “Our mission is to improve access to advanced treatments at attainable prices,” said Richard Daniell, executive vice president of Teva Europe Commercial in a news release.

Iveric Bio Reports Post Hoc Analysis From GATHER1 GA Trial

■ A post hoc analysis evaluating the reduction in GA lesion growth observed in patients receiving Iveric Bio’s Zimura (avacincaptad pegol) as compared to patients receiving sham in the completed GATHER1 clinical trial was presented at the Retina World Congress, in Fort Lauderdale, Florida. The results analyze the reduction in GA lesion growth, in a subset of GATHER1 patients, based on the distance of a patient’s GA lesion from the foveal center at baseline. In line with the overall results of GATHER1, a reduction of GA lesion growth in patients receiving Zimura as compared to patients receiving sham was consistently observed across all baseline distances from the foveal center.

Glenn J. Jaffe, MD, chief of the retina division at Duke Eye Center, presented the analysis. In a news release, Dr. Jaffe said, “These results suggest that early administration of Zimura to patients with GA lesions, when the lesion is still farther away from the foveal center and is growing the fastest, may be most beneficial.”

Primary Endpoint Results Presented From DAZZLE Study

■ The year 1 primary endpoint results from Kodiak Sciences’ pivotal phase 2b/3 DAZZLE trial evaluating KSI-301, in treatment-naïve subjects with wet AMD, were presented at ARVO 2022, by Carl Regillo, MD, from the retina service at Wills Eye Hospital of Thomas Jefferson University in Philadelphia. DAZZLE randomized 559 participants to either KSI-301 5 mg on a flexible long-interval regimen or aflibercept 2 mg on a fixed short-interval regimen. The primary endpoint of the study was the average change in BCVA. Although KSI-301 demonstrated strong durability and was safe and well tolerated, it did not meet the primary efficacy endpoint of showing noninferior VA gains for subjects dosed on extended regimens compared to aflibercept given every 8 weeks.

Dr. Regillo reported that robust treatment effects can be observed with KSI-301 and that the treatment effect can be maintained at long intervals for most patients. However, he noted, the protocol design needed to better anticipate and accommodate high-need patients, and, consequently, phase 3 DME studies have been amended to strike a more conservative balance between high-need patients and durability.

Lineage Developing Photoreceptor Treatment for Vision Loss

■ Lineage Cell Therapeutics announced that it is developing photoreceptor neural cell (PNC) transplants for the treatment of vision loss due to photoreceptor dysfunction or damage and that it has filed for intellectual property protection covering the composition and methods for generating PNCs. Based on recent in vivo data generated using the company’s PNCs, these cells may be capable of forming reconstructed retina with high survivability and neural connectivity to surrounding functional layers. Notably, Lineage has demonstrated feasibility that could support a large-scale method for producing both types of photoreceptors.

Rami Skaliter, PhD, who leads the manufacturing function for Lineage, said in a news release, “We believe this will provide new opportunities for clinical, and ultimately commercial, production of photoreceptors in areas of large unmet need such as retinitis pigmentosa, Stargardt macular dystrophy, and retinal detachments.”

MeiraGTx Presents Data on AAV5-RPGR for X-linked RP

■ MeiraGTx Holdings reported additional clinical data from the phase 1/2 trial of botaretigene sparoparvovec (AAV5-RPGR), for the treatment of X-linked retinitis pigmentosa (XLRP) at ARVO 2022. Professor Michel Michaelides of Moorfields Eye Hospital and the UCL Institute of Ophthalmology, delivered the presentation. Patients in the multicenter, open-label trial were given AAV5-RPGR subretinally at 1 of 3 doses to the worse-seeing eye.

Professor Michaelides’ presentation revealed that improvements in photoreceptor function assessed through 12 months post treatment suggest local efficacy of AAV5-RPGR gene therapy in XLRP patients. He also reported that the treatment effect is observed within the treated bleb and may also extend beyond the margins of the bleb following surgery owing to subretinal extension before retinal reattachment.

MERLIN nAMD Study Terminated Due to Intraocular Inflammation

■ An update on the phase 3a trial of brolucizumab in participants with nAMD and persistent retinal fluid was recently published in the AAO’s journal Ophthalmology. The study’s authors reported that VA outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed every 4 weeks were noninferior to aflibercept 2 mg dosed every 4 weeks. However, incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were also higher, leading to termination of the study. The incidence of IOI was 9.3% for brolucizumab vs 4.5% for aflibercept.

At week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline, and visual stabilization or improvement occurred at comparable rates: 82.5% for brolucizumab and 82.0% for aflibercept, as did the gain of ≥15, ≥10, and ≥5 letters for brolucizumab (16.9%, 22.3%, and 35.8%, respectively) and aflibercept (17.4%, 20.2%, and 31.5% respectively). A total of 4.8% and 1.7% of participants reported ≥15-letter BCVA loss from baseline at week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared to those treated with aflibercept, the CST was significantly reduced (P<.001) and there was a significantly greater proportion of eyes that were fluid free at week 52 (40.4% brolucizumab vs 19.0% aflibercept).

Liquid Biopsy Predicts Mortality in Uveal Melanoma

■ Christina Herrspiegel, MD, and colleagues from the Karolinska Institute and St. Erik Eye Hospital in Stockholm, Sweden, reported that they have developed a prognostic test, referred to as serUM, that they believe is a strong predictor of metastasis of uveal melanoma (UM). According to the researchers, the test is based on serum obtained from peripheral blood samples at the time of diagnosis of uveal melanoma in 83 patients, from 1996 to 2000 at St. Erik Eye Hospital. All patients were diagnosed with primary melanoma in the choroid or ciliary body. The test was developed in a training cohort (n=17) and then validated in an independent cohort (n=62). Patients had gradually shorter metastasis-free survival (P=.02) and greater incidence of UM-related mortality in competing risk analysis with increasing metastatic risk category and (P=0.027). The authors concluded that “serUM … is a strong predictor of metastasis,” but they stressed the need for future prospective studies to validate the findings of the current study.

Promising Opregen Phase 1/2a Clinical Trial Results Reported

■ Lineage Cell Therapeutics announced 1-year primary endpoint safety and tolerability results in the ongoing phase 1/2a clinical study of Opregen, a retinal pigment epithelial cell therapy in development for the treatment of GA secondary to AMD. The data, which were delivered at ARVO by Allen C. Ho, MD, director of retina research at Wills Eye Hospital, support the potential for Opregen to slow, stop, or reverse disease progression in GA. Patients in cohort 4 (n=12) had an average 7.6 letter gain in VA at 12 months in the study eye. Five patients in cohort 4 had an average of 12.8 letter gain in VF, with apparent improvement of outer retinal structure. “These data, though uncontrolled, offer the promising demonstration that Opregen may be able to impact GA disease progression in a clinically meaningful manner, particularly when delivered on target and in earlier disease, in patients afflicted with what was previously thought to be an inevitably progressive disease,” Dr. Ho said in a news release.

Promising Gene Therapy for Rare Inherited Retinal Diseases

■ Opus Genetics announced promising new preclinical data from studies evaluating the potential of its gene therapies OPGx-001 and OPGx-002 for treatment of Leber congenital amaurosis (LCA), a group of rare inherited retinal diseases characterized by photoreceptor degeneration, due to mutations of LCA5 or RDH12 genes, respectively. The data demonstrate that despite severe retinal dysfunction, LCA patients exhibited detectable photoreceptor regions that may be targets for gene augmentation. The data support the therapeutic potential and tolerability of gene augmentation to address LCA5-LCA and RDH12-LCA and provide guidance for formal preclinical toxicology studies and future human clinical trials.

“The detection of preserved photoreceptors in LCA patients signals a therapeutic opportunity to target the mutation and potentially restore structure and function through gene augmentation,” said Ash Jayagopal, PhD, chief scientific officer of Opus, in a news release.

INTEGRAL Trial Fails to Show Efficacy in Key Endpoints

■ Oxurion NV announced top-line results from part A of INTEGRAL, its phase 2 trial of THR-687, an integrin antagonist, for the treatment of DME. The data showed THR-687 to be safe and well tolerated; however, there was insufficient evidence of efficacy on the key endpoints, BCVA and central subfield thickness. Consequently, Oxurion will not advance THR-687 to part B of the INTEGRAL trial.

The company is now fully focused on advancing THR-149, which recently demonstrated a compelling safety and efficacy profile in patients with DME in the first part of the 2-part phase 2 KALAHARI trial. THR-149 is a first-in-class therapeutic for the up to 50% of DME patients who suboptimally respond to the current standard of care. Tom Graney, CFA, CEO of Oxurion, said in a news release, “We remain committed to developing new treatments to address the substantial unmet needs that remain in retinal diseases, and are excited about the potential of THR-149.”

Study Shows Weak Correlation Between Provider and Patient Satisfaction

■ Surgeon and anesthesiologist satisfaction has been found to be an unreliable indicator of patient satisfaction during ocular surgery, according to a study performed at Boston Medical Center. Researchers found that only a low-level association was demonstrated between a patient and provider’s satisfaction with anesthesia, even when individual measures of patient satisfaction such as pain and anxiety were isolated.

Researchers analyzed 283 ophthalmic surgical cases where patients were sedated with benzodiazepine prior to the start of surgery and then were given supplemental anesthesia throughout the procedure, as needed. After surgery, the patients, surgeons, and anesthesiologist were all given surveys to assess their level of satisfaction. The correlation of patient-to-surgeon satisfaction was 0.333 on a scale of 0 to 1, indicating a moderately weak correlation. “If provider assessment is not reflective of patient comfort, patients may not be receiving adequate sedation throughout their procedures,” Hyunjoo Lee, MD, PhD, an ophthalmologist at Boston Medical Center, said in a news release.

Treat-and-Extend Promising for Radiation Retinopathy

■ Intravitreal injections of aflibercept (Eylea) given in a treat-and-extend regimen can stabilize VA and improve macular anatomy in eyes injured by radiation retinopathy, according to Stephanie Trejo Corona, BA, BS, a researcher at Retina Consultants of Texas, who reported on the study at ARVO 2022. The trial confirms the approach that most clinicians are using in treating radiation retinopathy.

“Given the similar clinical manifestations of radiation retinopathy with diabetic retinopathy, well-established diabetic retinopathy anti-VEGF treatments seem to be useful for the treatment of radiation retinopathy,” Trejo Corona said during the ARVO presentation. Patients were randomized to either a loading dose of 3 aflibercept injections or no loading dose. Injections were administered every 4 weeks, but the period was extended by 2 weeks if intraretinal and subretinal fluid appeared resolved on SD-OCT and loss of VA since the previous visit was less than 5 ETDRS letters.

The overall improvement of 4.09 letters was not statistically significant compared with baseline (P<.07), however, there was a statistically significant improvement in overall central retinal thickness, from 475.5 µm to 317.9 µm (P<.001), and VA of 20/200 or better was achieved by 97.1% of patients.

Subcutaneous Injections Safe in Healthy nAMD and DME Patients

■ Ashvattha Therapeutics presented safety data, in poster form, from a phase 1 study of D-4517.2, its potent VEGFR/PDGFR tyrosine kinase inhibitor conjugated to a hydroxyl dendrimer, at ARVO 2022. The data showed that single subcutaneous doses of D-4517.2 were safe and well tolerated, in healthy subjects, at dose levels of 0.25 mg/kg, 0.50 mg/kg, and 1.0 mg/kg.

“We are encouraged by the safety and tolerability data on D-4517.2 from the 3 cohorts and are currently recruiting the fourth cohort at a dose level of 2.0 mg/kg, and plan on initiating a phase 2 study in wet AMD and DME patients in the coming weeks,” said Jeffrey Cleland, PhD, chairman, CEO and president of Ashvattha Therapeutics, in a news release. He added, “We are advancing this first-in-class therapy to enable patients the convenience of self-administration with an autoinjector up to once a month in the comfort of their home.”

Suprachoroidal Drug Delivery Considered Viable by Retina MDs

■ Bausch + Lomb Corporation released findings from a survey designed to gain an understanding of retina specialists’ need for a new treatment option for patients with ME associated with noninfectious uveitis, and the new drug delivery method in which treatment is administered via the suprachoroidal space. Approximately 85% of retina specialists surveyed considered drug delivery via suprachoroidal space as an option for patients with ME associated with noninfectious uveitis, approximately 84% have high interest in learning more about it, and more than 90% said alternatives are needed to treat patients with this condition. Nearly 70 retina specialists completed the survey, which was conducted by Modern Retina.

In a news release, Christina Ackermann, president of ophthalmic pharmaceuticals at Bausch + Lomb, said the survey results underscore the significance behind the availability of Xipere (triamcinolone acetonide injectable suspension), the first and only treatment to be approved by the FDA for delivery via the suprachoroidal space.

Opthea Presents Data on Combo Therapy for PCV 

■ Data from Opthea Limited’s phase 2b study of OPT-302 in combination with ranibizumab, for polypoidal choroidal vasculopathy in patients with treatment naive exudative AMD, were presented at ARVO, by Jason Slakter, MD, clinical professor in the department of ophthalmology at NYU Grossman School of Medicine. In this study, subjects received either monotherapy with ranibizumab or combination therapy with ranibizumab and 1 of 2 doses of OPT-302. OPT-302 (2.0 mg), used in combination with ranibizumab (0.5 mg), achieved superior VA gains and anatomic improvements compared to monthly ranibizumab monotherapy. Of the 366 participants, 66 (18%) were identified as having PCV lesions at baseline. Analysis of OPT-302 combination therapy over 6 months revealed an additional 6.7-letter gain was achieved over ranibizumab monotherapy, a greater proportion of patients gained ≥10 and ≥15 letters from baseline, or achieved 20/40 vision or better, while fewer participants lost 5 letters or more of vision.