Progress in Therapy for Geographic Atrophy

Educational Objectives

The goal of this program is to improve the diagnosis and management of age-related macular degeneration (AMD). After hearing and assimilating this program, the clinician will be better able to:

1. Evaluate data on investigational therapies that may slow the progression of geographic atrophy.

Summary

Overview: there is a large unmet need for treatment of advanced dry AMD, which is characterized by geographic atrophy (GA); progression of GA lesions is persistent and irreversible; evidence suggests excessive complement activation as the causative mechanism

Pegcetacoplan: C3 target; cyclic peptide conjugated to a polyethylene glycol molecule that targets C3

Phase 3 studies: randomized >1200 patients to 2 different doses of pegcetacoplan vs sham with a primary endpoint of 12 mo; inclusion criteria included foveal and extrafoveal GA as well as fellow choroidal neovascularization; OAKS — met the primary endpoint; rate of progression of GA was slowed by 22% with monthly treatment with pegcetacoplan and ≈16% with treatment every 2 mo, compared with the sham arm; DERBY — did not meet the primary endpoint; a prespecified combined analysis of both studies shows that progression of extrafoveal lesions slowed by ≈26% with monthly injection in a dose-dependent manner, and the incidence of wet AMD increased in a dose-responsive manner

Avacincaptad: C5 target; GATHER1 — results indicate progression of extrafoveal lesions is slowed by ≈28%, varying among the quadrants around the fovea; post hoc analysis indicates that earlier treatment can slow the progression of drusen to incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) or complete RORA (cRORA) by ≈19.6%, as well as slow the progression of iRORA to cRORA

Gene therapy: complement factor I (CFI) and CFH are highly associated with AMD; variants in CFI and CFH amplify the complement system

GT005: uses an adeno-associated virus serotype 2 vector to deliver a wild-type variant of CFI and induce its constitutive expression; delivered via a transvitreal subretinal procedure; FocuS — data show a 122% increase in CFI levels in the vitreous and 46% reduction in biomarkers; rare variants of CFI have increased risk for disease progression; restoring homeostasis reduces the C3 level by ≈32%; follow-up through 84 wk finds continued expression of CFI

Readings

Jaffe GJ, Westby K, Csaky KG, et al. C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: a randomized pivotal phase 2/3 trial. Ophthalmology. 2021;128(4):576-586. DOI:10.1016/j.ophtha.2020.08.027; Nanegrungsunk O, Au A, Sarraf D, et al. New frontiers of retinal therapeutic intervention: a critical analysis of novel approaches. Ann Med. 2022;54(1):1067-1080. DOI:10.1080/07853890.2022.2066169; Rubner R, Li KV, Canto-Soler MV, et al. Progress of clinical therapies for dry age-related macular degeneration. Int J Ophthalmol. 2022;15(1):157-166. DOI:10.18240/ijo.2022.01.23.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Holekamp’s lectures include information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Holekamp spoke at the 15th Annual Retina Symposium, presented by the University of Illinois College of Medicine, Department of Ophthalmology and Visual Sciences, held virtually on March 11, 2022. For information about upcoming CME conferences from this presenter, please visit: cemedicine.uic.edu. Audio Digest thanks the speakers and the University of Illinois College of Medicine for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

Lecture ID:

OP601603

Qualifies for:

ABO Continuing Certification

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.