Aldeyra Therapeutics Plans to Submit NDA for Drug for Primary Vitreoretinal Lymphoma

■ Aldeyra Therapeutics announced imminent plans to submit an NDA to the FDA for the investigational drug ADX-2191 for the treatment of primary vitreoretinal lymphoma. ADX-2191, which has received FDA Orphan Drug Designation for the treatment of primary vitreoretinal lymphoma, is a novel, vitreous-compatible formulation of methotrexate. The planned NDA submission is expected to include a combination of published literature on the safety and efficacy of methotrexate for the treatment of primary vitreoretinal lymphoma and safety data from the recently completed phase 3 GUARD trial of ADX-2191 in proliferative vitreoretinopathy. During the phase 3 GUARD trial, ADX-2191 was well tolerated and there were no observed treatment-emergent serious adverse events.

Aldeyra intends to request priority review designation, which reduces the review period in which the FDA aims to take action on an NDA to within 6 months compared to 10 months under standard review.

“Pending FDA review, ADX-2191 could be the first FDA-approved therapy for primary vitreoretinal lymphoma, a rare but potentially fatal cancer with a median survival of less than 5 years,” Todd C. Brady, MD, PhD, Aldeyra president and CEO, said in a news release.

Alimera Abstracts Highlight Consensus Among Retina Specialists

■ Alimera Sciences presented findings demonstrating a high level of agreement among retina specialists on the role of inflammation in the pathophysiology of diabetic retinopathy (DR) and diabetic macular edema (DME), injection burden and patient adherence, and efficacy and safety of Iluvien (fluocinolone acetonide intravitreal implant) 0.19 mg sustained-release intravitreal implant, at the 2022 meeting of the Retina Society. The company also announced analysis of data from the 36-month PALADIN study that found 0.19 mg fluocinolone acetonide (FAc) provides long-term reduction of retinal thickness variability (RTV), which is correlated to improved visual outcomes and better disease control.

According to an abstract presented by Anton Kolomeyer, MD, PhD, a survey completed by 56 US retina specialists revealed consensus on the following statements: chronic low-grade inflammation and associated inflammatory cytokines (VEGF, IL-6, etc.) are key drivers of DR/DME pathogenesis; steroids have broad, nonspecific anti-inflammatory properties, including the downregulation of VEGF production; chronic low-grade inflammation can lead to neurodegenerative changes in DR; high injection burden tied to use of short-acting therapies may lead to lack of adherence; poor patient adherence can lead to increased amplitude and frequency of retinal fluctuations; the 0.19 mg FAc implant can minimize retinal thickness fluctuations and reduce treatment burden through continuous and consistent treatment over 36 months; and IOP elevation associated with the 0.19 mg FAc implant is manageable in the majority of cases with topical IOP lowering therapy.

In related news, according to an abstract presented by Veeral Sheth, MD, MBA, data from the PALADIN phase 4, real-world observational study support that the FAc implant significantly reduces RTV through reduction of the recurrence of edema.

Cognition Proposes Phase 2 Trial of CT1812 for Geographic Atrophy

■ Cognition Therapeutics presented the scientific rationale, supporting proof-of-concept data, and design of its planned phase 2 trial of CT1812 in geographic atrophy (GA) secondary to dry AMD, at the 2022 Dry AMD Therapeutic Development Summit. CT1812 is an experimental oral sigma-2 (σ-2) receptor modulator currently in phase 2 clinical trials for both Alzheimer disease and dementia with Lewy bodies. An unbiased pathway analysis from 2 Alzheimer disease clinical trials identified GA and macular degeneration as 2 diseases most significantly associated with proteomic changes in CT1812-treated vs placebo-treated patient biofluids. Based on several lines of evidence including these clinical proteomic analyses and preclinical data in retinal pigment epithelial cell models, Cognition has entered discussions with the FDA to initiate a phase 2 clinical trial in more than 200 people with GA.

“Complement inhibition has shown potential in clinical trials but must be given via intravitreal injection to each affected eye. We believe that a noninvasive oral therapeutic with a novel mechanism of action that can penetrate the blood-retina barrier and treat both eyes simultaneously would be a significant advantage to the millions of people at risk for permanent vision loss,” Lisa Ricciardi, president and CEO of Cognition Therapeutics, said in a news release.

Kiora Doses First Patient in ABACUS Study of KIO-301 for RP

■ Kiora Pharmaceuticals announced the dosing of the first patient in a first-in-human, open-label clinical trial for KIO-301, intended to restore vision loss in patients with retinitis pigmentosa (RP). KIO-301 is a visible, light-sensitive small molecule that acts as a reversible “photoswitch,” specifically designed to restore the eyes’ ability to perceive and interpret light in visually impaired patients. KIO-301 selectively enters retinal ganglion cells (those downstream of degenerated rods and cones) and “switches” them into light-sensing cells, capable of signaling the brain as to the presence or absence of visible light.

The ABACUS study will enroll 6 patients and evaluate 12 eyes. The first cohort of 3 patients will include individuals with no or bare light perception due to the progression of RP. The second cohort will include patients able to detect hand motion and count fingers. This single-site study is being conducted at the Royal Adelaide Hospital (RAH) in Adelaide, South Australia.

“An ability to demonstrate safety in this first-in-human study will be a big step forward in establishing proof-of-concept for KIO-301 and photoswitches for retinal reanimation,” Brian M. Strem, PhD, Kiora president and CEO, said in a news release.

RetinAI Launches AI Platform to Accelerate RWE Research and Analysis

■ RetinAI Medical announced that it has launched Discovery CORE, an artificial intelligence (AI) software platform that aims to accelerate data analysis by helping clinical and academic researchers collaborate more efficiently, in real time, on medical and imaging data sets. The software measures retinal fluid volumes and layer thickness across OCT data sets automatically, and it integrates annotation tools and electronic case report forms, enabling data insights to be shared across peer networks. The functionality of CORE can be used to assess disease endpoints at scale, jumpstart the building of registries and real-world evidence data sets, and help with shared workflows to evaluate data, train physicians, and establish best practices within the clinic.

Discovery CORE uses RetinAI’s CE-marked fluid and layer segmentation AI models to quickly visualize and generate measures such as fluid volumes and retinal layer thickness on optical coherence tomography volumes. With the AI model for fluid segmentation, CORE measures volumes for subretinal and intraretinal fluid, and pigment epithelium detachment. The AI model for layer segmentation measures total retinal thickness as well as layer thickness for 6 individual layers of the retina, including the photoreceptor and retinal pigment epithelium layer.

Genentech Launches Phase 2a Study of Patients With GA Secondary to AMD

■ Lineage Cell Therapeutics announced that its partner Genentech has launched a phase 2a multicenter, open-label, single-arm clinical study of RG6501 (OpRegen), a retinal pigment epithelial cell therapy. The study is intended to optimize subretinal surgical delivery and evaluate the safety and activity of OpRegen in approximately 30 and up to 60 patients with GA secondary to AMD. A key secondary objective is to evaluate the proportion of patients with qualitative improvement in retinal structure, as determined by SD-OCT, within 3 months following surgery. Study treatment will consist of a single subretinal injection of OpRegen at a dose of up to approximately 200,000 cells delivered to target areas of GA in the study eye.

“In our phase 1/2a clinical trial, OpRegen demonstrated the potential to slow, stop, or reverse the progression of GA … We expect the findings from this phase 2a study will be highly informative and may increase the probability of success in any future larger, comparative trials,” Brian M. Culley, Lineage CEO, said in a news release.

OpRegen is currently being developed under an exclusive worldwide collaboration between Lineage Cell Therapeutics, Roche, and Genentech. Genentech is a member of the Roche group.

Radius Gets Innovation Award for Wearable Diagnostic Device

■ Radius XR was named a CES 2023 Innovation Awards honoree, in both the Digital Health and Virtual & Augmented Reality categories, for a portable vision diagnostic and patient engagement system that combines diagnostics, business management, and patient education tools in a single wearable device. The system helps medical professionals diagnose patients and reduce staff workload by enabling patients to perform self-guided vision exams, with minimal supervision. The announcement was made at the CES 2023 influential technology event in Las Vegas.

Radius is the industry’s lightest wearable device and has the look and feel of a pair of sunglasses. The compact, lightweight design enables exams to be conducted anywhere, including the waiting room, eliminating the need to shuttle patients between machines, which can be challenging for individuals with mobility or vision issues.

“Radius expands on our commitment to vision health by providing the eye-care industry with an easy-to-use wearable device capable of performing standard perimetry tests (visual fields). Other exams include color vision, visual acuity, and contrast sensitivity,” Radius founder and CEO Ammad Khan said in a news release.

The CES Innovation Awards program, owned and produced by the Consumer Technology Association (CTA), is an annual competition honoring outstanding design and engineering in 27 consumer technology product categories.

UCLA-led Study Says Verteporfin May Also Help Fight COVID

■ An interdisciplinary team led by UCLA researchers found that verteporfin stopped the replication of SARS-CoV-2, the virus that causes COVID-19. The study, which was published in PLO in Biology, identified the Hippo signaling pathway as a potential target for therapies against the coronavirus. The findings indicate verteporfin may be a candidate to treat COVID-19, and its status as an FDA-approved drug could make it easier to launch clinical trials to verify its safety and effectiveness against the coronavirus.

The scientists observed changes in many genes involved with the Hippo signaling pathway after infection. In addition, they examined a protein called YAP, or Yes-associated protein, whose activity is blocked when the Hippo pathway is activated. They found that in cultured human cells, both the original strain and Delta variant of SARS-CoV-2 activated the Hippo pathway in the first few days after infection. When they silenced this pathway and increased YAP, the virus replicated itself more.

The team also pretreated cells with verteporfin, which blocks YAP in choroidal neovascularization, and then infected them with SARS-CoV-2. In the verteporfin-treated cells, concentrations of the coronavirus were below detectable levels, compared to more than 60,000 units of the virus per milliliter, in an untreated control group.

SparingVision Gets IND for Retinitis Pigmentosa Drug SPVN06

■ SparingVision announced that the FDA has cleared the company’s IND for SPVN06, its gene-independent therapy for the treatment of retinitis pigmentosa (RP). This IND paves the way for the initiation of PRODYGY (Promising Rod Cone Dystrophy Gene Therapy) a first-in-human, phase 1/2 study to assess the safety, tolerability, efficacy, and quality of life following a single subretinal injection of SPVN06 in the worst-seeing eye of adult patients with RP due to a mutation in the RHO, PDE6A, or PDE6B genes.

The primary endpoint of PRODYGY, which will recruit up to 33 patients, is the safety and tolerability of SPVN06, 12 months after administration of a single injection. The first safety data are anticipated in 2023, and the primary endpoint is expected to be reached in 2025.

“Receiving IND clearance is a testament to the incredible efforts of everyone at SparingVision. With over 80 genes involved in RP, each with numerous causative mutations, we need to go beyond the gene-by-gene treatment approach. SPVN06 has the potential to become the universal therapeutic solution that patients need, and we are excited for the next phase of development,” Stéphane Boissel, president and CEO of SparingVision, said in a news release.

SparingVision has also submitted a clinical trial authorization application for SPVN06 to the French regulatory agency ANSM, and it is under review.

Aflibercept Outperformed Bevacizumab in Wet AMD Retrospective Study

■ A pilot retrospective study of wet AMD has revealed that nearly half of patients treated with aflibercept could safely stop eye injection therapy after 1 year, without further vision loss, whereas only 17% of patients taking bevacizumab were able to safely wean from the drug at 1 year. The paper was published online in the Journal of Clinical Investigation.

In the study, researchers reviewed records of the treatment outcomes of 106 people with wet AMD who were treated at the Johns Hopkins Wilmer Eye Institute between 2013 and 2020, in 2 Maryland locations. The findings build on previous evidence that showed potentially one-third of patients with wet AMD could safely pause therapy after 1 year of monitoring by a physician.

“Our results suggest that if we can match the right patient to the best therapy, many patients with macular degeneration may not need lifelong therapy. These results provide additional evidence that aflibercept and bevacizumab should not be considered interchangeable when treating AMD,” Akrit Sodhi, MD, PhD, said in a news release. Dr. Sodhi is associate professor of ophthalmology and the Branna and Irving Sisenwein Professor in Ophthalmology at the Wilmer Eye Institute at the Johns Hopkins University School of Medicine. Clinical trials with a larger group of patients will be necessary to confirm these findings.

Retrospective Study Highlights Value of ARD Digital Remote Monitoring

■ Notal Vision has announced that results from the second report of the Analysis of Long-term Visual Outcomes of ForeseeHome Remote Telemonitoring (ALOFT) study were published in Ophthalmology Retina. The first published report of the ALOFT study analyzed data from more than 2,000 patients over 10 years, from 5 clinical sites. In the ALOFT study, patients self-tested with the ForeseeHome (Notal Vision) device, which uses a functional test to detect preferential hyperacuity perimetry (PHP). An intrinsic feature of the test detects changes in visual function, which prompts a monitoring center to alert the referring physician. The physician then determines if the alert was a conversion to wet AMD through a follow-up exam using diagnostic imaging.

The second report is the result of researchers in the ALOFT study group further analyzing the data from patients who had alerts that did not result in an immediate wet AMD diagnosis. These patients were twice as likely as other dry AMD patients to convert over the same period. The finding was even more remarkable for patients who had wet AMD in one eye and dry in the other eye. They had a 44% chance of converting to wet AMD over the next 2 years.

“We placed an increased focus on patients who were seen after a ForeseeHome alert, but at the time did not present with wet AMD,” Allen C. Ho, MD, the report’s principal author and the director of retina research at Wills Eye Hospital in Philadelphia, Pennsylvania, said in a news release. “In cases like these,” he explained, “patient management should include more frequent office visits given the elevated risk of conversion the home test indicates.”

CMS Assigns Permanent J-Code to Vabysmo for Wet AMD and DME

■ Genentech Ophthalmology announced that CMS issued a permanent J-code (J2777) for the bispecific antibody Vabysmo (faricimab-svoa), a vascular endothelial growth factor (VEGF) inhibitor and angiopoietin-2 that is administered as an intravitreal injection for wet AMD and DME. The J-Code is recognized by the government and commercial payors, and Genentech directs eye care providers to bill 60 units for the 6-mg administered dose of Vabysmo.

Genentech recently released data from 2 global phase 3 studies, BALATON and COMINO, evaluating the bispecific antibody in macular edema due to branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). The BALATON study is being conducted in 553 people with BRVO, and the COMINO study is being conducted in 729 people with CRVO or hemiretinal vein occlusion. Both studies met their primary endpoints, showing that people with macular edema due to BRVO and CRVO receiving Vabysmo injections every 4 weeks, for up to 24 weeks, achieved noninferior visual acuity gains compared to those receiving aflibercept injections every 4 weeks.

Optogenetics May Help Restore Neuronal Function in Neurologic Diseases

■ The optogenetic stimulation of human retinal ganglion cells by a light-projection system linked to a camera is a promising way to partially restore vision in blind patients affected with advanced retinitis pigmentosa (RP), according to a study published in Nature Medicine. In a blind patient, researchers combined intraocular injection of an adeno-associated viral vector encoding ChrimsonR with light stimulation via engineered goggles that detect local changes in light intensity and project corresponding light pulses onto the retina, in real time, to activate optogenetically transduced retinal ganglion cells. The patient perceived, located, counted, and touched different objects using the vector-treated eye alone while wearing the goggles. During visual perception, multichannel electroencephalographic recordings revealed object-related activity above the visual cortex. The patient could not visually detect any objects before injection with or without the goggles or after injection without the goggles. This is the first reported case of partial functional recovery in a neurodegenerative disease after optogenetic therapy.

The proof of concept for GS030-DP and the GS030-DP dose used in the PIONEER clinical trial were established in nonhuman primate studies. The scientists, led by José-Alain Sahel, MD, distinguished professor and chairman of the department of ophthalmology at the University of Pittsburgh School of Medicine, described their research as follows in the Nature Medicine paper: “Optogenetic vision restoration is a mutation-independent approach for restoring visual function at the late stages of RP after vision is lost. The open-label phase 1/2a PIONEER study was designed to evaluate the safety (primary objective) and efficacy (secondary objective) of an investigational treatment for patients with advanced non-syndromic RP that combines injection of an optogenetic vector (GS030 drug product) with wearing a medical device, namely light-stimulating goggles (GS030 medical device).” RP