Recap of Retinal Disease News from the 2022 Meeting of the American Academy of Ophthalmology
Eye On the Cure Research News
Reports on emerging therapies for dry age-related macular degeneration (geographic atrophy), Stargardt disease, and X-linked retinitis pigmentosa are included
The American Academy of Ophthalmology’s (AAO) Annual Meeting was held in Chicago from September 30 through October 3, 2022, and included a number of announcements and press releases on emerging therapies for retinal degenerative diseases. Here is a recap of the highlights:
Atsena Therapeutics LCA1 (GUCY2D) Gene Therapy improves Vision in Phase 1/2 Clinical Trial
Christine Kay, MD, from Vitreo Retinal Associates in Gainesville, Florida, reported positive results from Atsena’s Phase 1/2 gene therapy clinical trial for people with Leber congenital amaurosis type 1 (LCA1), which is caused by mutations in the gene GUCY2D. Overall, the gene therapy, ATSN-101, was well tolerated. The nine patients receiving the highest dose of ATSN-101 had clinically meaningful vision improvements as measured by a full-field stimulus test (FST), which measures the patient’s ability to respond to different levels of light, and by their ability to navigate a multi-luminance mobility course. Atsena is funded through the Foundation’s RD Fund, a venture philanthropy fund for emerging therapies in, or moving toward, early stage clinical trials.
Apellis Reported 24-Month Data for the Phase 3 Trials of its Geographic Atrophy Drug
The company continued to report meaningful reductions in the growth rate of geographic lesions — the regions of cell loss from advanced dry age-related macular degeneration (geographic atrophy) — in eyes treated with pegcetacoplan. Furthermore, the effect of the drug, a C3 protein inhibitor, increased over time. At 24 months in combined Phase 3 trials, foveal lesion growth slowed by 19 percent with monthly treatments and 16 percent with treatments every other month. Extrafoveal lesion growth slowed by 26 percent with monthly treatments and by 22 percent with treatments every other month. The fovea is a tiny pit in the central retina that provides the sharpest visual acuity. Apellis has filed a new drug application with the US Food & Drug Administration (FDA). A response from the FDA is expected by the end of November 2022.
Iveric Bio Presented Results from its Second Phase 3 Trial for Geographic Atrophy Drug
Iveric Bio, a company targeting unmet therapeutic needs for retinal diseases, reported on GATHER2, its second Phase 3 clinical trial for Zimura, an emerging treatment to slow the progression of geographic atrophy, the advanced form of dry age-related macular degeneration. Zimura is designed to inhibit the complement protein C5. GATHER2 is a global study that enrolled 448 patients. At 12 months, monthly intravitreal injections of Zimura reduced the growth rate of atrophic lesions (regions of retinal cell loss) by 14.3 percent in GATHER2. In GATHER1, the company’s previous global Phase 3 clinical trial for Zimura, patients had a 27.7 reduction in the growth rate of atrophic lesions. GATHER1 enrolled 286 patients. Iveric Bio plans to file a New Drug Application (NDA) with the US Food and Drug Administration by the end of the first quarter of 2023.
Belite Bio Presented One-Year Data from Phase 2 Clinical Trial for Stargardt Disease
Professor John Grigg, the study’s principal investigator from the University of Sydney, presented one-year, interim results for 13 patients (ages 12-18) in Belite’s two-year, Phase 2 clinical trial of Tinlarebant, an emerging oral treatment for Stargardt disease. The Phase 2 trial is ongoing in Australia and Taiwan. Nine of 13 patients had stabilization or improvement in visual acuity. The company also reported that the annual average growth rate of atrophic lesions — the areas of retinal cell loss — were significantly less than the growth rates observed in ProgStar, the Foundation-funded natural history study of Stargardt disease patients. Belite Bio is also conducting a global Phase 3 clinical trial for Tinlarebant in adolescent patients (ages 12-18). Tinlarebant is designed to reduce the uptake of vitamin A into the retina, thereby reducing the accumulation of toxic vitamin A byproducts, which are the hallmark of Stargardt disease.
MeiraGTx-Janssen Presented Results from Phase 1/2 Clinical Trial for X-Linked Retinitis Pigmentosa Gene Therapy
Professor Michel Michaelides, from University College London and Moorfields Eye Hospital, presented results from gene therapy developer MeiraGTx’s Phase 1/2 X-linked retinitis pigmentosa (RPGR) gene therapy ( botaretigene sparoparvovec) clinical trial, which set the stage for the Phase 3 LUMEOS clinical trial, which is currently underway. In the Phase 1/2 trial, improvements in retinal sensitivity were measured using full-field static perimetry and microperimetry. Walk time improved for patients navigating a low-luminance mobility course.
Janssen Presented Results from Phase 1 Clinical Trial for Geographic Atrophy Gene Therapy
Janssen reported encouraging data from its 17-participant Phase 1 Clinical Trial for its geographic atrophy (GA) gene therapy delivered through a single intravitreal injection. GA is the advanced form of dry age-related macular degeneration. The low, intermediate, and high doses of the GA gene therapy were safe over a two-year follow-up period. The company also reported continual decline in growth of lesions, the regions of retinal cell loss. Janssen plans to continue evaluation of the GA gene therapy in a clinical trial.
Opus Genetics Plans to Submit IND to FDA for LCA5 Gene Therapy
In an interview during the Eyecelerator meeting that preceded the AAO event, Ben Yerxa, PhD, chief executive officer at Opus Genetics, reported plans for the company to submit an investigational new drug (IND) application to the FDA by the end of 2022 for its LCA5 (lebercillin) gene therapy. The IND, if authorized, would enable Opus to launch its planned Phase 1/2 for the emerging treatment. The company is also in preclinical development for gene therapies for LCA13 (RDH12) and LCA9 (NMNAT1). Opus is funded through the Foundation’s RD Fund, a venture philanthropy fund for emerging therapies in, or moving toward, early stage clinical trials.