TY - JOUR
T1 - Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2)
T2 - 12-month results from a randomised, double-masked, phase 3 trial
AU - GATHER2 trial investigators
AU - Khanani, Arshad M.
AU - Patel, Sunil S.
AU - Staurenghi, Giovanni
AU - Tadayoni, Ramin
AU - Danzig, Carl J.
AU - Eichenbaum, David A.
AU - Hsu, Jason
AU - Wykoff, Charles C.
AU - Heier, Jeffrey S.
AU - Lally, David R.
AU - Monés, Jordi
AU - Nielsen, Jared S.
AU - Sheth, Veeral S.
AU - Kaiser, Peter K.
AU - Clark, Julie
AU - Zhu, Liansheng
AU - Patel, Hersh
AU - Tang, Justin
AU - Desai, Dhaval
AU - Jaffe, Glenn J.
AU - Alezzandrini, Arturo
AU - Francone, Anibal Andres
AU - Bafalluy, Joaquín
AU - Bainttein, Silvina
AU - Luna Pinto, Jose
AU - Saravia, Mario
AU - Vidosevich, Matko
AU - Zeolite, Carlos
AU - Furno Sola, Federico
AU - Chang, Andrew
AU - Cornish, Elisa Eleanor Guida
AU - Nguyen, Thanh
AU - Findl, Oliver
AU - Haas, Anton
AU - Kralinger, Martina
AU - Sacu, Stefan
AU - Postelmans, Laurence Dominique
AU - Farah, Michel
AU - Maia, Mauricio
AU - Nehemy, Marcio
AU - Ali, Fareed
AU - Brent, Michael
AU - Dollin, Michael
AU - Gonder, John
AU - Kherani, Amin
AU - Merkur, Andrew
AU - Tuli, Raman
AU - Lopera, Monica Marie
AU - Rodriguez, Francisco
AU - Chang, Emmanuel
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/10/21
Y1 - 2023/10/21
N2 - Background: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. Methods: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 μL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366. Findings: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016–0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group. Interpretation: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy. Funding: Iveric Bio, An Astellas Company.
AB - Background: Geographic atrophy is an advanced form of dry age-related macular degeneration that can lead to irreversible vision loss and high burden of disease. We aimed to assess efficacy and safety of avacincaptad pegol 2 mg in reducing geographic atrophy lesion growth. Methods: GATHER2 is a randomised, double-masked, sham-controlled, 24-month, phase 3 trial across 205 retina clinics, research hospitals, and academic institutions globally. To be eligible, patients had to be aged 50 years or older with non-centrepoint-involving geographic atrophy and best corrected visual acuity between 20/25 and 20/320 in the study eye. Eligible patients were randomly assigned (1:1) to monthly avacincaptad pegol 2 mg administered as a 100 μL intravitreal injection or sham for the first 12 months. Randomisation was performed using an interactive response technology system with stratification by factors known to be of prognostic importance in age-related macular degeneration. Patients, investigators, study centre staff, sponsor personnel, and data analysts were masked to treatment allocation. The primary endpoint was geographic atrophy lesion size measured by fundus autofluorescence at baseline, month 6, and month 12. Efficacy and safety analyses were done in the modified intention-to-treat and safety populations, respectively. This trial is registered with ClinicalTrials.gov, NCT04435366. Findings: Between June 22, 2020, and July 23, 2021, 1422 patients were screened for eligibility, of whom 448 were enrolled and randomly assigned to avacincaptad pegol 2 mg (n=225) or sham (n=223). One patient in the sham group did not receive study treatment and was excluded from analyses. There were 154 (68%) female patients and 71 (32%) male patients in the avacincaptad pegol 2 mg group, and 156 (70%) female patients and 66 (30%) male patients in the sham group. From baseline to month 12, the mean rate of square-root-transformed geographic atrophy area growth was 0·336 mm/year (SE 0·032) with avacincaptad pegol 2 mg and 0·392 mm/year (0·033) with sham, a difference in growth of 0·056 mm/year (95% CI 0·016–0·096; p=0·0064), representing a 14% difference between the avacincaptad pegol 2 mg group and the sham group. Ocular treatment-emergent adverse events in the study eye occurred in 110 (49%) patients in the avacincaptad pegol 2 mg group and 83 (37%) in the sham group. There were no endophthalmitis, intraocular inflammation, or ischaemic optic neuropathy events over 12 months. To month 12, macular neovascularisation in the study eye occurred in 15 (7%) patients in the avacincaptad pegol 2 mg group and nine (4%) in the sham group, with exudative macular neovascularisation occurring in 11 (5%) in the avacincaptad pegol 2 mg group and seven (3%) in the sham group. Interpretation: Monthly avacincaptad pegol 2 mg was well tolerated and showed significantly slower geographic atrophy growth over 12 months than sham treatment, suggesting that avacincaptad pegol might slow disease progression and potentially change the trajectory of disease for patients with geographic atrophy. Funding: Iveric Bio, An Astellas Company.
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U2 - 10.1016/S0140-6736(23)01583-0
DO - 10.1016/S0140-6736(23)01583-0
M3 - Article
C2 - 37696275
AN - SCOPUS:85175498187
SN - 0140-6736
VL - 402
SP - 1449
EP - 1458
JO - The Lancet
JF - The Lancet
IS - 10411
ER -