C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial
- PMID: 32882310
- DOI: 10.1016/j.ophtha.2020.08.027
C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial
Abstract
Purpose: The complement pathway may play a key role in the pathogenesis of age-related macular degeneration (AMD). The safety and efficacy of avacincaptad pegol (Zimura, IVERIC bio Inc, New York, NY), a C5 inhibitor, were assessed in participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study).
Design: International, prospective, randomized, double-masked, sham-controlled, pivotal phase 2/3 clinical trial.
Participants: A total of 286 participants with GA secondary to AMD.
Main outcome measures: The primary efficacy endpoint was the mean rate of change in GA over 12 months measured by fundus autofluorescence (FAF) at 3 timepoints: baseline, month 6, and month 12.
Results: The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4% (P = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8% (P = 0.0051) for the avacincaptad pegol 4 mg cohort compared with their corresponding sham cohorts. The results for both dose groups were statistically significant. Avacincaptad pegol was generally well tolerated after monthly administration over 12 months. There were no avacincaptad pegol-related adverse events (AEs) or inflammation. Further, there were no ocular serious AEs (SAEs) and no cases of endophthalmitis. The most frequent ocular AEs were related to the injection procedure.
Conclusions: Intravitreal administration of avacincaptad pegol 2 mg and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 12-month period. Because C5 inhibition theoretically preserves C3 activity, it may offer additional safety advantages. A second confirmatory pivotal clinical trial is underway to confirm the efficacy and safety of avacincaptad pegol in slowing the GA growth (GATHER2 Study).
Keywords: C5 inhibitor; Complement; GATHER1; GATHER2; Zimura; age-related macular degeneration; avacincaptad pegol; dry; geographic atrophy.
Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Comment in
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Reply.Ophthalmology. 2021 May;128(5):e26-e27. doi: 10.1016/j.ophtha.2020.12.031. Epub 2021 Feb 5. Ophthalmology. 2021. PMID: 33551285 No abstract available.
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Re: Jaffe et al.: C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration: a randomized pivotal phase 2/3 trial (Ophthalmology. 2021;128:576-586).Ophthalmology. 2021 May;128(5):e25-e26. doi: 10.1016/j.ophtha.2020.12.030. Epub 2021 Feb 4. Ophthalmology. 2021. PMID: 33551286 No abstract available.
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Re: Jaffe et al.: C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration (Ophthalmology. 2021;128:576-586).Ophthalmology. 2021 Dec;128(12):e219. doi: 10.1016/j.ophtha.2021.08.018. Epub 2021 Sep 29. Ophthalmology. 2021. PMID: 34600774 No abstract available.
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Reply.Ophthalmology. 2021 Dec;128(12):e219-e220. doi: 10.1016/j.ophtha.2021.08.019. Epub 2021 Sep 29. Ophthalmology. 2021. PMID: 34600775 No abstract available.
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Two studies to learn if avacincaptad pegol works and is safe in people with geographic atrophy: a plain language summary of the GATHER1 and GATHER 2 studies.Immunotherapy. 2024 Mar;16(4):205-221. doi: 10.2217/imt-2023-0274. Epub 2024 Jan 25. Immunotherapy. 2024. PMID: 38270081
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