Eylea HD 1-year Pivotal Data Published in The Lancet
Regeneron announced that 1-year results from the pivotal PULSAR and PHOTON trials for Eylea HD (aflibercept) injection 8 mg have been published in The Lancet. The published data demonstrate that Eylea HD extended dosing regimens were noninferior to Eylea (aflibercept) injection 2 mg for both the treatment of wet AMD and DME. PULSAR and PHOTON are 2 double-masked, active-controlled pivotal trials evaluating Eylea HD compared to Eylea. Both PULSAR in wAMD (N=1,009) and PHOTON in DME (N=658) met their primary endpoints, with Eylea HD demonstrating noninferior and clinically equivalent vision gains at 48 weeks — with both 12-week and 16-week dosing regimens after 3 initial monthly doses — compared to an Eylea 8-week dosing regimen after initial monthly doses (3 in PULSAR and 5 in PHOTON).
Ophthalmology Biotech Company Launches to Advance Retinal Gene Therapies
Ophthalmology biotech PulseSight Therapeutics announced its launch backed by seed finance from Pureos Bioventures and ND Capital. PulseSight plans to advance 2 first-in-class late-stage preclinical drugs for wet and dry AMD. The company’s proprietary nonviral gene therapy ocular platform uses an electrotransfection system to deliver DNA plasmids encoding therapeutic proteins into the ciliary muscle to treat major eye diseases. The technology has already been validated in a first phase 1/2 clinical study, demonstrating a good safety profile of both the plasmid and the delivery system, as well as a long-lasting clinical benefit up to 8 months in patients with chronic noninfectious uveitis.
The company’s lead program, PST-809, is a potential first-in-class therapy for wet AMD that comprises a dual-gene plasmid encoding for a potent anti-VEGF. Its second program, PST-611, for geographic atrophy (GA) in late-stage dry AMD, uses the same disruptive delivery technology.
Inflammation-reducing Drug Shows No Benefit for Dry AMD in NEI Phase 2 Trial
A phase 2 clinical study sponsored by the National Eye Institute (NEI) demonstrated that minocycline failed to slow vision loss or expansion of geographic atrophy (GA) in people with dry AMD. The study tested whether inhibiting microglia with minocycline might help slow GA expansion. Researchers led by Tiarnan Keenan, MD, PhD, of the NEI’s Division of Epidemiology and Clinical Applications, enrolled 37 participants. After a 9-month period where the researchers tracked each participant’s rate of GA expansion, the participants took twice-daily doses of minocycline for 2 years. The researchers compared each participant’s rate of GA expansion while taking minocycline to their baseline rate and found there was no difference in GA expansion rate or vision loss with minocycline.
Microglia, immune cells that help maintain tissue and clear up debris, are present at higher levels around damaged retinal regions in people with dry AMD than in people without AMD. Scientists have suggested that inflammation — and particularly microglia — may be driving the expansion of GA regions. Previous studies have shown that minocycline can help reduce inflammation and microglial activity in the eye, including the retina. The drug has shown beneficial effects for diabetic retinopathy but has not previously been tested for dry AMD.
Restoret Is Well Tolerated in Patients With DME and Neovascular AMD
Eyebiotech announced first-in-human phase 1b/2a AMARONE trial results of Restoret in patients with treatment-naive DME and treatment-naive neovascular AMD. The 12-week results showed that Restoret, an investigational trispecific Wnt agonist antibody, was well-tolerated, with no drug-related adverse events, drug-related serious adverse events, or intraocular inflammation. The analysis was presented by Charles C. Wykoff, MD, at the Macula Society Meeting in Palm Springs, California. Patients with DME (n=26) received Restoret as monotherapy, manifesting a mean improvement in BCVA of +11.2 letters and a mean reduction in retinal thickness of -143 μm, as measured by OCT. Similar outcomes were observed in patients with wet AMD (n=5), who received Restoret in combination with aflibercept. The data demonstrated that multiple monthly doses of Restoret, as both monotherapy and in combination with aflibercept, were well tolerated.
Study Shows AI System Has Perfect Detection Rate for ROP
The i-ROP Deep Learning system, which uses an artificial intelligence (AI) algorithm to identify blood vessel anomalies in retinal images, can accurately and independently detect 100% of severe cases of retinopathy of prematurity (ROP), according to a study from Oregon Health and Science University (OHSU) and collaborators, published in JAMA Ophthalmology. For this study, the AI system analyzed nearly 12,000 images of more than 4,000 infants’ retinas. Ophthalmologists had previously reviewed the images as part of telemedicine programs and found that about 1.2% of the infants had severe forms of ROP, while about 5.8% had more-than-mild cases. The AI system correctly identified all of the severe cases and accurately detected 80% of the cases with more-than-mild ROP. The i-ROP system was initially developed by researchers from OHSU, Massachusetts General Hospital, Northeastern University, University of Illinois, Chicago and the Imaging and Informatics in ROP, or i-ROP, consortium.
“This paper demonstrates that AI can effectively replace the physician for bedside screening and refer the most urgent cases to a physician for treatment,” the study’s corresponding author, J. Peter Campbell, MD, said in a news release. Dr. Campbell is also CEO of Siloam Vision, which licensed the technology and is currently leading clinical trials to evaluate the AI system’s safety and effectiveness.
Bausch + Lomb Presents Xipere Data at Macula Society Meeting
Bausch + Lomb presented outcomes of a study designed to understand durability of suprachoroidal triamcinolone acetonide injectable suspension (Xipere) and subsequent practice patterns for treatment of uveitic macular edema in clinical practice, at the annual Macula Society Meeting. The study cohort included 750 patients and 831 eyes. Overall, 24.6% of patients required a corticosteroid (12.3% topical only) in the 24 weeks after suprachoroidal triamcinolone acetonide. By comparison, rescue therapy was required by 13.5% of patients in the clinical trial, despite the use of a second, protocol-driven suprachoroidal triamcinolone acetonide injection at week 12 that was not counted as rescue. A second injection around week 12 does not appear to be part of routine clinal practice, because only 2.4% of eyes had an injection in that timeframe.
Nearly 50% of patients had a history of glaucoma or ocular hypertension, which is higher than the previously reported prevalence of glaucoma, suggesting that suprachoroidal triamcinolone acetonide may be used preferentially in this population due to compartmentalization of the drug away from other tissues, potentially reducing risk of certain side effects. Future analyses to understand the impact of triamcinolone acetonide on intraocular pressure are under way. Xipere is the first and only treatment to be approved in the United States for delivery via the suprachoroidal space.
GenSight Announces Lumevoq Gene Therapy Study Results
GenSight reported initial efficacy and safety results from the REFLECT phase 3 clinical trial with Lumevoq (lenadogene nolparvovec) for Leber hereditary optic neuropathy. The data indicate that that after 1-time administration of the gene therapy, visual acuity (VA) improvement was maintained over 4 years in all subjects, with the VA of bilaterally injected patients remaining better than that of patients who received unilateral injection. Overall, 73% of bilaterally treated patients had a VA improvement of at least 15 letters. A favorable safety profile at 4 years was confirmed as well.
“The sustained effect on vision, as observed in the REFLECT trial, is a crucial piece of the Lumevoq story for patients, physicians, and health authorities. The durable impact from a single administration differentiates gene therapy from other treatment modalities, facilitating patient adherence and improving quality of life,” Laurence Rodriguez, CEO of GenSight Biologics, said in a news release.
GenSight also reported results of new meta-analyses showing that Leber hereditary optic neuropathy patients treated with Lumevoq experienced a rate of visual recovery greater than that of idebenone-treated patients and untreated patients. The meta-analyses consisted of 5 natural history studies (173 patients), 6 idebenone studies (201 patients) and 3 Lumevoq studies (174 patients). The results were reported at the 2024 meeting of the North American Neuro-Ophthalmology Society.
Sex Disparities in Ophthalmology, From Training Through Practice, Analyzed
A systematic review of females in ophthalmology, from training through practice in high-income countries, revealed that an increase in the proportion of females in the field over the past 3 decades was not associated with an increase in female representation in leadership positions, and sex disparities in the experiences of females in ophthalmology were identified at all career stages. The review, published in JAMA Ophthalmology, included 87 cross-sectional studies and 4 cohort studies. Among the findings: in medical school, mentorship, and recruitment of female students into ophthalmology was influenced by sex bias, with fewer females identifying with ophthalmologist mentors, and gender stereotypes perpetuated in reference letters written by both male and female referees. In residency, females had unequal learning opportunities, with lower surgical case volumes than male trainees and fewer females pursued fellowships in lucrative subspecialties. In practice, female ophthalmologists had lower incomes, less academic success, and poorer representation in leadership roles.
Findings of relevance to the vitreoretinal specialty include: during fellowship, females had lower volumes for specific procedures — namely internal limiting membrane peel, scleral buckle, and cryoretinopexy. Also, vitreoretinal meetings with at least 1 female committee member had more female invited speakers and invited moderators and panelists. The researchers concluded that there is a need for active interventions to address sex disparities in ophthalmology to improve equity in this field.
Topical Eyedrop for Retinal Disease Shows Safety and Tolerability
Exonate announced data from a successful phase 1b/2a trial for EXN407, a topical formulation that selectively targets and inhibits VEGF. The mild/moderate nonproliferative diabetic retinopathy (NPDR) and mild diabetic macular edema (DME) clinical study assessed the safety, tolerability, and signals of biological response to EXN407 monotherapy in a double-masked, placebo-controlled phase 1b/2a dose-ranging clinical trial in treatment-naïve patients with NPDR and DME. The data demonstrate the safety and tolerability of EXN407, as well as clear indications of biological activity, positioning it well for further development as the first topical treatment for retinal vascular diseases.
An independent dose escalation committee characterized EXN407 as safe and well tolerated, with 100% of patients completing the study without requiring anti-VEGF rescue. The study concluded that there were promising signals of biological response from EXN407, demonstrating sustained decreases in macular thickness, relative to the placebo group and comparable to previously reported anti-VEGF injections.
“The results suggest that topical ocular EXN407 may provide clinical benefit and substantially reduce the injection burden for patients with diabetic eye disease,” Catherine Beech, CEO, Exonate, said in a news release. Exonate is now planning to progress EXN407 to the Clinical Evaluation of a New Eyedrop for Alleviating Retinopathy in Diabetic Macular Edema (CLEAR-DM) phase 2b clinical trial. RP
In Brief
Burnout among ophthalmologists decreased by 9% in the last year, according to Medscape’s 2024 “Physician Burnout and Depression Report.” Although 48% of surveyed ophthalmologists said they experienced burnout in the 2023 report, 39% reported burnout in the 2024 report. Ophthalmology was tied for second to last among 25 specialties ranked by burnout in the 2024 report, down from number 12 in 2023. Meanwhile, overall physician burnout decreased from 53% to 49% between the 2023 and 2024 reports. The survey noted that burnout is the top factor contributing to physician depression.
Eye care private equity deals have decreased dramatically, according to Pitchbook’s “Healthcare Services Report,” published in February. The number of private equity-driven deals in vision — including add-on, platform, and growth deals — decreased by 43% between 2022 and 2023. The total number of health care–focused private equity deals overall decreased by 16.2% in 2023. Numerous scaled platforms, including vision, are languishing under significant debt burdens, making few acquisitions — and only small ones. Add-on deal activity declined by more than 50% year-over-year in vision, according to the report.
The next resupply mission to the International Space Station (ISS) will carry more than 40 payloads sponsored by the ISS National Laboratory, including technology demonstrations and life science experiments. Among the research is an investigation from biopharmaceutical company Oculogenex, which will use its mission to the ISS to test a novel gene therapy to prevent and possibly even reverse vision loss from AMD. The investigation aims to find out if gene therapy can thwart spaceflight-induced retinal dysfunction and degeneration. “The microgravity investigation could pave the way for future clinical trials and treatments, offering hope to those grappling with this debilitating condition,” said Hema Ramkumar, CEO of Oculogenex, in a news release.
Ocugen announced that dosing is complete in the first cohort of its phase 1/2 ArMaDa clinical trial for OCU410 — a modifier gene therapy candidate being developed for geographic atrophy (GA). The ArMaDa clinical trial will assess the safety of unilateral subretinal administration of OCU410 in subjects with GA. “While there are currently 2 recently approved products for the treatment of GA, both require approximately 6 to 12 intravitreal injections annually and target only the complement system. OCU410 addresses multiple pathways causing dry AMD, including complement, lipid metabolism, inflammation, and oxidative stress,” Shankar Musunuri, PhD, chairman, CEO and cofounder of Ocugen, said in a news release.
Rehabilitation training can improve visual function and real-world tasks, such as reading skills, in patients with late-stage AMD, who are implanted with the smaller-incision new-generation miniature telescope (SING IMT), according to a study. The study included 11 patients who were monocularly implanted with SING IMT and then followed a rehabilitation program. Both reading acuity and reading speed were found to be significantly improved from the first rehabilitation session (6 weeks after surgery) to the last session (24 weeks after surgery), and most patients (55%) achieved an improvement of 15 letters in BCDVA at the end of the study.
Iveric Bio, an Astellas company, announced that CMS has assigned a unique, permanent Healthcare Common Procedure Coding System (HCPS) J-code for Izervay (avacincaptad pegol intravitreal solution) for the treatment of GA secondary to AMD. The new J-code, J2782, which became effective April 1, is expected to accelerate patient access in the United States. “Receiving a permanent J-code in the US supports our efforts to increase timely patient access to IZERVAY, the first and only FDA-approved GA treatment to demonstrate a statistically significant reduction in the rate of GA progression in just 12 months across 2 pivotal trials,” Michael Petroutsas, Astellas, Head of US Commercial, said in a news release.
Doheny Eye Institute announced the publication of a paper detailing groundbreaking findings regarding the cause of Leber hereditary optic neuropathy (LHON). The study, performed by Doheny scientists with colleagues at UCLA and University of Texas, was published in the journal Proceedings of the National Academy of Sciences. The team compared molecular interactions in LHON mutated protein and showed that electron transfer to coenzyme Q10 is massively slowed, creating conditions favorable for the production of cell-damaging reactive oxygen species, which provides an explanation of how the mutation disrupts mitochondrial function, initiating a cascade that may lead to blindness.
