IN BRIEF

Research and industry news in retina.

BY JERRY HELZNER, CONTRIBUTING EDITOR

Lineage Gets $24.6 Million Cash Infusion

Lineage Cell Therapeutix, developer of OpRegen cell technology for the treatment of dry AMD, said it received $24.6 million in cash from Juvenescence Ltd., representing funds due under a convertible promissory note. The note was issued as partial payment for the sale by Lineage to Juvenescence of 14.4 million shares of common stock of AgeX Therapeutics, Inc.

“With an additional $24 million just received from Juvenescence, we believe we have over two years of cash runway based on our current business plan. This cash runway extends well past the expected timing of several major clinical milestones,” stated Brian M. Culley, Lineage CEO.

Ophthalmic Bevacizumab Trial Shows Early Efficacy

Outlook Therapeutics announced top-line results demonstrating anticipated safety and efficacy and positive proof-of-concept of ONS-5010/LYTENAVA (bevacizumab-vikg) for the treatment of wet AMD from its 25-patient NORSE 1 clinical study, the first of 2 registration clinical trials. ONS-5010 is the first injectable ophthalmic formulation of bevacizumab-vikg seeking FDA approval for the treatment of wet AMD under a new Biologics License Application (BLA).

“Although a small study, we are excited to see that both the efficacy signals that we anticipated in NORSE 1 for an ophthalmic bevacizumab as well as the clinical safety data are consistent with previously published results for ophthalmic bevacizumab,” stated Mark Humayun, MD, PhD, medical advisor to Outlook Therapeutics. “We are looking forward to seeing the results of the NORSE 2 pivotal trial in the third quarter of 2021. If ONS-5010 is approved to treat wet AMD and other retinal diseases, it will be a significant development in the practice of ophthalmology. Bevacizumab is a well understood anti-VEGF therapy that is already widely used, and ONS-5010, if approved, will be a valuable, FDA-approved treatment option across the spectrum of retinal care.”

The company also announced that, as part of its phase 3 program, it has enrolled the first patients in a supplemental safety trial evaluating ONS-5010. This trial will ensure that enough patients have been exposed to ONS-5010 to support the planned new BLA filing with the FDA next year.

Developing an approved ophthalmic formulation of bevacizumab is important to meet the medical needs of the roughly 50% of wet AMD patients who currently are treated with unapproved repackaged IV bevacizumab supplied by compounding pharmacists. These off-label drugs carry risks posed by a lack of sterility, safety, consistent potency and availability. If ONS-5010 is approved, it will be the first and only on-label ophthalmic formulation of bevacizumab-vikg and will offer an approved and responsibly priced anti-VEGF therapy across the spectrum of retinal care.

LumiThera Gets NIH Grant to Study DR

LumiThera Inc., a commercial-stage medical device company creating a photobiomodulation (PBM) treatment for ocular disorders and disease, is a recipient of a small business innovative research (SBIR) phase 2 grant from the National Institute of Health (NIH) and the division of the National Eye Institute (NEI). The grant supports a prospective, randomized, multicenter human clinical trial in US subjects diagnosed with diabetic retinopathy (DR) and diabetic macular edema (DME). The PRIME trial, which is subject to FDA Investigational Device Exemption approval, will test vision and examine disease pathology in the eye following PBM treatments using the Company's Valeda Light Delivery System. Subjects will be followed for up to 6 months. In 2018, LumiThera obtained a CE mark to commercialize the Valeda Light Delivery System in Europe for the treatment of dry AMD.

LumiThera is also collaborating with Diopsys, a leading provider of modern visual electrophysiology solutions, in the ELECTROLIGHT study. Diopsys' technology helps eye care professionals accurately and objectively measure retinal and visual pathway function. The joint effort will support a pilot human clinical trial for subjects diagnosed with dry AMD. The study will evaluate the ability of PBM treatment using the Valeda Light Delivery System to improve electroretinogram outcomes.

Macular Hole Surgery: The Earlier, the Better

■ In a retrospective review conducted by a multinational group of European researchers and led by Matteo Fallico of the University of Catania, Italy, 27.8% of 327 patients who underwent anatomically successful macular hole surgery had normal vision defined as BCVA ≥20/25 at 1 year. The most salient factor associated with achieving normal vision was shorter duration of symptoms, with normal vision achieved in 70.6% of eyes operated within 1 week vs 45% of eyes operated after 1 to 3 weeks of symptoms. Other associated factors were smaller preoperative OCT minimum linear diameter and better mean preoperative BCVA. The researchers concluded that prompt surgery is justified for smaller macular holes of short duration. Their findings appeared in Acta Ophthalmologica.

Sealing Large, Persistent Macular Holes

■ Bio-Tissue, Inc. announced positive outcomes in a case series detailing surgical repair of 8 of 10 large macular holes (MHs) using AmnioGraft Cryopreserved Amniotic Membrane. The study, published in Ophthalmic Surgery, Lasers and Imaging Retina, showed that the placement of AmnioGraft may be a feasible alternative to conventional surgical methods to improve anatomic and visual outcomes. Large, persistent MHs and MH retinal detachment can cause severe visual impairment, especially in highly myopic eyes. Conventional surgical methods have variable outcomes in terms of closure rates and visual recovery.

AmnioGraft was used in 10 patients with significant (1229.30 μm ± 774.54 μm), persistent, or primary MHs in a recent interventional case series from Taiwan. After at least 6 months, 8 cases (80%) had sealed MHs, and none of the eyes showed signs of infection, inflammation, or rejection.

In another recent review, the graft improved the BCVA in 2 cases of chronic, refractory, large MHs. One of the patients was a 65-year old female with a 1,310 μm diameter MH of 3 years’ duration that had previously failed repair. After repair with AmnioGraft, the patient’s visual acuity improved from 20/100 to 20/60 with the closure of the MH at 2 weeks and an improving retinal morphology at 10 weeks.

Levodopa May Combat Advanced AMD

■ Investigators have determined that treatment with the Parkinson disease drug levodopa in patients with advanced AMD stabilized and improved patients’ vision. In the study of AMD, levodopa reduced the number of treatments necessary to maintain vision, and as such, could reduce the burden of treating the disease, financially and otherwise. The findings appear in the American Journal of Medicine.

Earlier research found that patients treated with levodopa for movement disorders such as Parkinson disease were significantly less likely to develop AMD. Lead investigator Robert W. Snyder, MD, PhD, explained, “Levodopa has a receptor (GPR143) selectively expressed on pigmented cells. This receptor can be supportive of retinal health and survival, which led to the development of our hypothesis that it may prevent or treat AMD.”

Santen Acquires Eyevance to Round Out Product Offerings

■ In a move to expand its product portfolio to the anterior segment and also increase its US presence, Santen has acquired Eyevance Pharmaceutical for $225 million in cash. Santen Holdings U.S. Inc., a wholly owned subsidiary of Santen, will acquire all of the outstanding shares of Eyevance Pharmaceuticals Holdings. Eyevance will become a wholly owned subsidiary of Santen.

Founded in 2017, Eyevance develops and commercializes topical ophthalmic products targeting the ocular surface and anterior segment. Eyevance currently offers anti-inflammatory, anti-allergic, antifungal, anti-infective/anti-inflammatory fixed combination, and tear lubricant products.

Gyroscope Gets Fast Track for Geographic Atrophy Therapy

■ Gyroscope Therapeutics Limited, a clinical-stage retinal gene therapy company, announced that the FDA has granted Fast Track designation to GT005 for the treatment of geographic atrophy (GA) secondary to dry AMD. GT005 is an investigational one-time AAV-based gene therapy delivered under the retina and is intended to slow the progression of GA that can lead to blindness. The designation was granted to GT005 for people with GA who have specific mutations in their complement factor I (CFI) gene and low levels of the CFI protein in their blood. Enrollment in the phase 2 EXPLORE study to evaluate GT005 in this group of people is under way.

Neurophth Gets Orphan Drug Status for LHON Therapy

■ Neurophth Therapeutics announced that its leading candidate, NR082, was granted orphan drug designation by the FDA for the treatment of Leber hereditary optic neuropathy (LHON) associated with ND4 mutation.

LHON is a maternally inherited mitochondrial disease characterized by acute or subacute painless vision loss, or even loss simultaneously or sequentially, accompanied by central visual field defect and color vision impairment with poor prognosis. It affects about 100,000 people worldwide and is a blinding disease. The disease mainly occurs in young and middle-aged males. Currently, there is no effective treatment for LHON. About 70% to 90% of LHON is caused by ND4 mutation. With the development of NR082, AAV-based gene therapy of LHON becomes possible, according to the company.

“NR082 is the first candidate drug developed by Neurophth. It uses recombinant adeno-associated virus serotype 2 to deliver the genetically modified ND4 gene (rAAV2-ND4),” Alvin Luk, PhD, CEO of Neurophth, said in a company news release. “After a single intravitreal injection, the gene is translated and expressed in cells, and this effectively supplements the functional loss caused by endogenous mutation. Through this gene therapy, the electron transport function of mitochondrial respiratory chain was maintained, and the increase of ATP synthesis restored the normal function of mitochondria, which in turn improved the sensory function of the retinal ganglion cells and improved the visual acuity of LHON patients.”

Neurodegenerative Biomarker Identified in Vitreous

■ A new study led by Boston Medical Center researchers indicates a well-known biomarker that serves as a marker for earlier diagnosis of neurodegenerative diseases is detectable in the eye. Neurofilament light chain, a protein previously detected in cerebrospinal fluid and blood that is being explored as a biomarker to detect neurodegeneration, has now been identified in the vitreous humor. Published in Alzheimer’s Research & Therapy, these results set a foundation for future studies to investigate the potential of this biomarker to accelerate the diagnosis of Alzheimer disease, Parkinson disease, and other neurodegenerative diseases.

Beovu Effective Against Early Persistent Fluid

■ Novartis said results of 2 new post-hoc analyses of the phase 3 HAWK and HARRIER clinical trials in wet AMD were presented at the EURETINA 2020 virtual congress. The first analysis demonstrated fewer Beovu (brolucizumab) patients had early persistent fluid, defined as the presence of intraretinal fluid and/or subretinal fluid through week 12 of treatment, compared with aflibercept patients. For patients who did have early persistent fluid, those treated with Beovu achieved greater BCVA gains and greater reductions in central subfield thickness (CST) at week 96 than those treated with aflibercept.

A second analysis showed Beovu was associated with better control of retinal fluid, as measured by achievement and maintenance of defined CST levels. In the study, more Beovu patients than aflibercept patients achieved CST control (80% for Beovu and 69% for aflibercept at week 96 at a defined CST threshold of 320 µm). Patients who stayed longer in a controlled CST state had better visual gains compared with those who remained in an uncontrolled CST state.

Elderly RRD Outcomes Less Favorable

■ A large-scale US multicenter comparative cohort study was launched to describe characteristics and outcomes of primary rhegmatogenous retinal detachment (RRD) in older adults (age ≥80). Consecutive patients with RRD undergoing pars plana vitrectomy (PPV), scleral buckling (SB), or PPV/SB in the Primary Retinal Detachment Outcomes Study were evaluated. Outcome measures included single surgery anatomic success (SSAS) and visual acuity (VA).

Of 2,144 patients, 125 (6%) were 80 years or older. Compared to younger patients (age 40-79), older adults were more likely to be pseudophakic, have macula-off detachments, and have preoperative proliferative vitreoretinopathy. In older adults, initial surgery was PPV in 73%, PPV/SB in 27%, and primary SB in 0%. SSAS was 78% in older adults and 84% in younger patients. In older adults, SSAS was 74% for PPV and 91% for PPV/SB. Final mean logMAR was lower for older adults (0.79 [20/125] vs 0.40 [20/40]). In older adults, final mean logMAR for eyes that underwent PPV was 0.88 (20/160) compared to 0.50 (20/63) for PPV/SB. Octogenarians and nonagenarians presented with relatively complex pseudophakic RRDs. SSAS and visual outcomes were worse compared to younger patients, and PPV/SB had better outcomes compared to PPV alone. The findings were reported in the journal Retina.

Eyevensys Gets Orphan Status for RP Therapy

■ Eyevensys said the FDA has granted an orphan-drug designation for EYS611 for the treatment of retinitis pigmentosa (RP). Eyevensys is developing EYS611, a DNA plasmid that encodes for the human transferrin protein, to benefit patients diagnosed with RP, as well as other degenerative retinal diseases, including late-stage dry AMD and glaucoma.

Transferrin is an endogenous protein that helps manage iron levels in the eye. While iron is essential for retinal metabolism and the visual cycle, excessive iron can induce oxidative stress and is extremely toxic to the retina. Iron overload has been associated with photoreceptor death in several retinal degenerative diseases. By acting as an iron chelating and neuroprotective agent, EYS611 helps slow the progression of diseases like RP, regardless of the specific genetic mutation causing the condition.

Teleophthalmology App Effective in Military Consults

■ Military doctors have developed a mobile app that permits remote consults to quickly evaluate the seriousness of eye trauma. Of the first 28 consults conducted in Afghanistan, 24 were deemed correct diagnoses that were confirmed by ophthalmologists who later saw the patients in person.

The accuracy of the initial diagnoses prevented the need for aeromedical evacuation in 4 cases and allowed a quicker return to duty in 15 cases. Overall satisfaction with the app was rated by users at the maximum score of 5. RP