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The FDA has accepted Regeneron Pharmaceuticals’ supplemental Biologics License Application (sBLA) of aflibercept (Eylea) injection for review in patients with diabetic retinopathy (DR).

According to a news release from the company, the regulatory agency has set a target action date of February 28, 2023.

Regeneron noted that the supplemental Biologics License Application (sBLA) is supported by data readout from the Phase 3 PANORAMA trial investigating every 8- and 16-week aflibercept dosing regimens, versus sham, in patients with severe non-proliferative diabetic retinopathy (NPDR) without diabetic macular edema (DME).

Additionally, the filing was further supported by clinical data from the NIH-sponsored Protocol W trial evaluating an aflibercept every 16-week dosing regimen in patients with moderate to severe NPDR without center-involved DME versus sham.

If approved by the regulators, the aflibercept every 16-week dosing regimen could offer certain patients a potentially longer treatment interval and doctors with greater flexibility to individualize treatment.

Articles

The FDA has accepted the supplemental Biologics License Application of aflibercept injection for review in patients with diabetic retinopathy.

FDA accepts Regeneron’s aflibercept injection submission for review

RegeneRx Biopharmaceuticals Inc. said today that its U.S. joint venture (JV) partner and licensee, HLB Therapeutics (HLBT), is planning to expand its ophthalmic clinical development program with RGN-259 in two indications, neurotrophic keratopathy (NK) and dry eye disease (DED), beginning in November.

The trials will be sponsored by the U.S. JV, ReGenTree, LLC.

In a news release, the companies noted that RGN-259 is a sterile, preservative-free, eye drop developed to reduce damage and improve healing for various ophthalmic indications including dry eye syndrome and neurotrophic keratopathy.

To date, more than 1700 subjects have received RGN-259 indicating various degrees of efficacy in both DED and NK. RGN-259 has shown to be quick-acting, well-tolerated and does not have the documented side effects of other approved pharmaceutical products for these indications.

According the HLBT, it will run both DED and NK clinical development program simultaneously. In the case of DED, for which ReGenTree conducted a pre-BLA meeting in February this year, the company said it plans to apply for SPA (Special Protocol Assessment) to the FDA around this October. SPA is a program in which FDA specialists provide a sponsor (ReGenTree) with collaboration in setting up clinical protocols and statistical analysis plans.

The agreed clinical trial design with FDA is binding and this program will give the sponsor and FDA a clear understanding [of relevant trial criteria] by participating together at this stage of the clinical trial protocol development.

The company also noted in its news release that ReGenTree will start the two phase 3 trials for NK simultaneously [to meet the requirement of two independent phase 3 clinical trials necessary for FDA marketing approval].

HLBT also noted that ReGenTree will seek to confirm the efficacy observed in SEER-1 despite the very small number of subjects in that trial. Based on the results of the SEER-1 study, ReGenTree has developed a plan to enter into two phase 3 studies (SEER-2, SEER-3) simultaneously with 60 patients in each study. To this end, it plans to retain a contract research organization (CRO) very shortly and start recruitment of patients in November.

J.J. Finkelstein, RegeneRx's president and CEO, said the company was pleased to see that HLBT is moving forward with both NK and DED clinical trials with RGN-259.

“We believe our product candidate has significant potential as an important therapeutic modality for numerous ophthalmic disorders,” he said in a news release. “Accelerating NK clinical development by simultaneously conducting two trials will speed up the process while also working with the FDA under an SPA to refine our approach to DED. I believe this strategy indicates that HLBT is fully committed to RGN-259's clinical development in the field of ophthalmology.”

RegeneRx Biopharmaceuticals Inc. said its U.S. joint venture partner and licensee, HLB Therapeutics, will expand its ophthalmic clinical development program with RGN-259 in two indications, neurotrophic keratopathy and dry eye disease.

RegeneRx licensee to expand Phase 3 clinical trial program with RGN-259

A specific cell within the retina appears to be particularly good at housing Ebola and other viruses, new research has found.1

A highly infectious and lethal viral disease, Ebola was first observed 1976 and has since impacted thousands of humans and animals, primarily in Central Africa.

“Inflammation of the eye, known as uveitis, is very common following infection with Ebola and we know the cells within the iris, at the front of the eye, as well as the retina have the capacity to play a major role in uveitis and act as hosts for microorganisms,” says study senior author P Justine Smith, PhD, FARVO, a strategic professor in Eye and Vision Health at Flinders University. “However, what we didn’t know was which out of the two was most responsible in the case of Ebola.”

The study wasled by Flinders University and CSIRO’s Australian Centre for Disease Preparedness, used cells from human eyes donated from the SA Eye Bank to investigate the ability of iris and retinal pigment epithelial cells to be infected by Ebola.

According to a news release from Flinders University, cells were infected with Ebola virus, Reston virus (a type of 

 that does not cause disease in humans) or Zika virus (another type of virus, but one that also can cause uveitis), while some were left uninfected for the duration of the trial.

While both types of cells seemed to allow the Ebola virus to replicate, it was the retinal cells that showed much higher levels of infection.

“We also found similar results when looking at the cells infected with Reston virus and Zika virus,” Smith said in the release.

Moreover, Smith explained that patients with Ebola eye disease have characteristic retinal scars, suggesting the retinal pigment epithelium is involved in the disease, so this finding is consistent with what eye doctors are seeing in the clinic.

“These retinal cells are good at eating things – called phagocytosis - and they play an essential part in the visual cycle by recycling our photoreceptors, so it makes sense that these cells would be a receptive haven for Ebola, as well as other viruses,” she noted.

According to the university, the researchers explained that the study demonstrates an important target cell for Ebola infection in the eye and suggests the potential for these cells to be monitored during acute viral infection to identify patients at highest risk of uveitis.

“Amongst other issues, including pain and blurred vision, uveitis can ultimately lead to vision loss, so it’s important we find ways to diagnose it as early as possible to enable swift treatment,” Smith concluded.

The work was supported by a grant from the National Health & Medical Research Council.

1 Shawn Todd, Yuefang Ma, Liam M. Ashander, Binoy Appukuttan, Michael Z. Michael, Timothy A. Blenkinsop, Steven Yeh, Glenn A. Marsh and Justine R. Smith

Ebola virus differentially infects human iris and retinal pigment epithelial cells. Frontiers in Virology

A team of investigators at Flinders University in Australia have found that a specific cell within the retina appears to be particularly good at housing Ebola and other viruses.

Eyes a haven for Ebola and other viruses

Dry eye disease (DED) continues to be a difficult problem for patients whose eyes do not provide adequate lubrication. The discomfort that results from dry eyes may affect vision, and if left untreated, the National Eye Institute (NEI), noted that it can damage the cornea.

Prevent Blindness has declared July as “Dry Eye Awareness Month” to provide free resources to providers and the public on dry eye, including fact sheets and shareable social media graphics in both English and Spanish, and a dedicated webpage.

Additionally, as part of the Focus on Eye Health Expert Series, Stephanie Marioneaux, MD, cornea and external disease specialist, and Prevent Blindness board of directors member, provides detailed information in the recent “

Mental health may also be affected by dry eye. A 

recent study published in JAMA Ophthalmology

 found that depression was associated with more severe dry eye symptoms and overall signs, suggesting that among patients with moderate to severe DED, those with depression may be likely to have more severe DED. According to the study conclusion, the findings support consideration of depression as a comorbidity when managing patients with DED.

Extreme sensitivity, especially to cigarette smoke

Having these symptoms may mean that you have dry eye, but they may also be caused by other conditions. A thorough evaluation by an eye doctor is needed to determine the exact cause of these vision symptoms.

“Dry eye can have lasting, damaging effects if left untreated,” said Jeff Todd, president and CEO of Prevent Blindness. “An exam by an eyecare professional can equip patients with a treatment plan that protects vision and improves mental health.”

For more information on dry eye, please visit the Prevent Blindness resource page at 

preventblindness.org/understanding-dry-eye

The organization hopes to increase awareness and education of a condition that affects vision, mental health. 

Prevent Blindness: July is Dry Eye Awareness Month

Notal Vision Inc. reported this week that several scientific and clinical presentations prove the feasibility and efficacy of their patient-operated, home-based optical coherence tomography (OCT) device.

According to the company, as part of a remote monitoring service, which includes a monitoring center and artificial intelligence algorithms for information processing, the OCT device (Notal Home OCT) monitors wet age-related macular degeneration (AMD) treatment between doctor’s office visits.

Wet AMD is the leading cause of blindness in people older than the age of 50 in the United States. Several treatments have been developed over the last 2 decades and have proven to be extremely beneficial. However, therapy requires frequent office visits for disease monitoring, placing a major burden on physicians, patients, and their caregivers. This burden has contributed to the limited real-world efficacy of these treatments.

The company noted that home monitoring using standard of care OCT technology is expected to optimize treatment regimens for these patients and provide better vision outcomes. The key challenges for home OCT technology include demonstrated correlation with in-office devices, full self-operation by the patients, convenient use in a home setting, continuous patient compliance, and the ability to extract meaningful information from the high-volume data being generated. The investigational OCT device, which received an FDA breakthrough designation, is a pipeline technology for monitoring wet AMD treatments.

A series of studies using the investigational OCT device have shown that the device is effective in overcoming each of these challenges. A prospective and cross-sectional study,

 which included 333 wet AMD patients and 600 eyes, demonstrated the ability of patients to self-image in a clinic setting, with over 91% of patients being able to successfully acquire images without technician assistance. The imaging showed excellent correlation with in-office OCT for detecting the presence of fluid, an important biomarker in wet AMD, with over 95% agreement.

“We were very surprised by Home OCT’s self-imaging success rate and the patient response,” said David Lally, MD, from the Retina Research Institute at New England Retina Consultants, Springfield, Massachusetts. “Patients with limited vision were able to self-image with no assistance, and most patients felt that use of the device was much easier than they initially anticipated. I think after imaging nearly 600 eyes with Home OCT, we can be confident in its capability to produce reliable images with patient self-operation.”

The company also noted in its release that a prospective and longitudinal study to understand patients’ ability to self-image in a home setting with no prior training was conducted by prominent retina specialists Jeffrey Heier, MD and Nancy Holekamp, MD.

According to the release, the program enrolled 15 wet AMD patients and the device was shipped to their homes by the Notal Vision Monitoring Center. Subjects were able to set up the device themselves and perform daily scans with the support of the Monitoring Center clinical staff.

Patients demonstrated extraordinary self-imaging capability, with a total of 2300 scans taken at a 95% success rate. Yingna Lui, MD recently presented the results from this study at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting, which also demonstrated the importance of home-based OCT data for better disease management in patients, reviewing specific remote monitoring case studies. The US study followed a prospective longitudinal pilot study conducted in Israel by Anat Loewenstein, MD and colleagues in 2020.

The release also noted that patient compliance was also studied in the Heier and Holekamp longitudinal study. Patients performed an average of 5.8 exams per week, demonstrating strong compliance to ensure any exudation of fluid, critical to wet AMD management, was promptly captured. Patients were asked to assess their satisfaction of the OCT device as part of the study and rated it neutral to highly satisfactory on over 95% of questions, and highly agreed on convenience and ease of use.

“The Notal Vision Monitoring Center shipped the device directly to patients and managed all their training and patient questions­ ­– no training was provided by our site,” said Heier, director of the retinal service and retinal research at Ophthalmic Consultants of Boston. “Physicians reviewed the AI-generated data from the device using a web-based viewer. This technology has the potential to allow clinicians daily assessment of fluid status, earlier recognition of recurrent activity, and can reduce the significant burden currently placed on patients, caregivers, and their providers.”

Home OCT cannot be adopted by doctors without the ability to distill the large volumes of images generated by the device into actionable information. This process is managed by the AI-powered Notal OCT Analyzer (NOA). Fluid regions captured by Home OCT’s B-scans are segmented and quantified by NOA and these volumes, an important biomarker in wet AMD, are studied over time. NOA’s performance was demonstrated by Michael Elman, MD and Sid Schechet, MD during a 26-patient study they conducted, in which patient self-acquired scans were analyzed using NOA and compared with expert-graded commercial OCT scans. Presented by Dr. Elman at the ARVO annual meeting, the results found a high correlation of over 97% between the NOA and manually graded OCT scans. This study further demonstrates the capability of the AI-based algorithm for fluid quantification in wet AMD patients.

“We are excited to see multiple investigators evaluating different aspects of our investigational Home OCT platform,” said Kester Nahen, PhD, CEO of Notal Vision. “This is further validation of the efficacy of our digital health-based remote monitoring model, which we currently use for the ForeseeHome AMD Monitoring Program. We believe we have perfected the various components of the model over the past ten years, which has greatly helped us bring this impactful technology closer to market.”

Notal Vision’s home-based OCT pipeline technology has received an FDA Breakthrough Device designation and is in the process of obtaining FDA clearance. In January 2020, the American Medical Association established three category III Current Procedural Terminology (CPT) codes for reporting patient-initiated remote retinal OCT scans, facilitated by Notal Vision’s home-based OCT.

The physician review, interpretation and documentation of AI-based analyses will be billable every 30 days.

Kim JE, Tomkins-Netzer O, Elman MJ, Lally DR, 

 Evaluation of a self-imaging SD-OCT system designed for remote home monitoring. 

https://doi.org/10.1186/s12886-022-02458-z

Liu Y, Holekamp NM, Heier JS. Prospective, Longitudinal Study: Daily Self-Imaging with Home OCT for Neovascular Age-Related Macular Degeneration. 

https://doi.org/10.1016/j.oret.2022.02.011

Keenan TDL, Goldstein M, Goldenberg D, Zur D, Shulman S, Loewenstein A, Prospective, Longitudinal Pilot Study Daily Self-Imaging with Patient-Operated Home OCT in Neovascular Age-Related Macular Degeneration. 

https://doi.org/10.1016/j.xops.2021.100034

Investigators show the effectiveness of Home-OCT based remote monitoring model. 

Efficacy of Notal Vision OCT device demonstrated by a series of scientific and clinical work

Oculis S.A. this week announced that the first patient has been enrolled in its Phase 3 OPTIMIZE (Once-daily Post ocular surgery Treatment for InflaMmation and paIn to minimiZE drops) trial evaluating the efficacy and safety of once-daily OCS-01, a novel, high concentration, preservative-free, topical optireach formulation of dexamethasone for the treatment of inflammation and pain following cataract surgery.

According to the company, in the completed Phase 2 SKYGGN study, once-daily OCS-01successfully met its primary endpoint demonstrating superior efficacy and safety vs vehicle (placebo) in the treatment of inflammation and pain following cataract surgery.

The company also noted that it subsequently held a positive end-of-Phase 2 meeting with U.S. FDA, which enabled the start of the Phase 3 OPTIMIZE trial.

OPTIMIZE is a randomly assigned, double-blind, placebo-controlled Phase 3 trial in 25 participating sites across the US and is scheduled to enroll approximately 240 patients. Efficacy measures of the trial include the absence of anterior chamber cells at Day 15 and absence of pain at Day 4.

Treatment of inflammation and pain following ocular surgery is another indication being pursued for OCS-01, following the commencement in November 2021 of the Phase 3 DIAMOND trial investigating OCS-01 in patients with DME.

Eric Donnenefeld, MD, clinical professor of ophthalmology at New York University and Trustee of Dartmouth Medical School, discussed the need for an effective option to treat inflammation after cataract surgery.

“Following cataract surgery, patients often need to self-administer eye drops several times a day to manage inflammation and pain,” he said in a statement. “An efficacious, preservative-free alternative, administered just once a day could provide significant advantages over current options.”

Moreover, Riad Sherif, MD, CEO of Oculis, pointed out that the start of the Phage 3 trial marks a key development milestone for OCS-01, following the start of the company’s Phase 3 trial in DME last year, which further signals the potential for this novel product candidate to address the limitations of currently available treatments for both retinal and front-of-the-eye indications.

“Clinical data generated so far have been very encouraging and we look forward to generating further data in this trial to support regulatory submissions,” Sherif said.

OCS-01 has been developed using Oculis’s OPTIREACH solubilizing nanoparticle technology, a proprietary platform that enables the formulation of drugs as non-invasive topical eyedrop treatments, a longer residence time on the eye surface and enhances their bioavailability in the relevant eye tissues, particularly the retina.

OCS-01 is being reviewed for the treatment of inflammation and pain after cataract surgery, with the potential to become the first once-daily, topical and preservative-free corticosteroid for treating inflammation and pain following ocular surgery. 