TY - JOUR
T1 - Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration
AU - CEDAR and SEQUOIA Study Groups
AU - Khurana, Rahul N.
AU - Kunimoto, Derek
AU - Yoon, Young Hee
AU - Wykoff, Charles C.
AU - Chang, Andrew
AU - Maturi, Raj K.
AU - Agostini, Hansjürgen
AU - Souied, Eric
AU - Chow, David R.
AU - Lotery, Andrew J.
AU - Ohji, Masahito
AU - Bandello, Francesco
AU - Belfort, Rubens
AU - Li, Xiao Yan
AU - Jiao, Jenny
AU - Le, Grace
AU - Kim, Kimmie
AU - Schmidt, Werner
AU - Hashad, Yehia
N1 - Funding Information:
R.N.K.: Consultant – Allergan (an AbbVie company), Alkahest, Apellis, Clearside Biomedical, Genentech, Merck, Regeneron; Financial support – Allergan (an AbbVie company), Apellis, Clearside Biomedical, Roche, Santen D.K.: Consultant – Allegro, Allergan (an AbbVie company), Genentech, GrayBug, Novartis, VisionCare; Financial support – Allergan (an AbbVie company), Genentech, GrayBug Y.H.Y.: Consultant – Alcon, Allergan (an AbbVie company), Bayer, Boehringer Ingelheim, Roche; Financial support – Allergan (an AbbVie company), Bayer, Roche C.C.W.: Consultant – Adverum, Aerpio, Alimera Sciences, Allegro, Allergan (an AbbVie company), Alnylam, Apellis, Bayer, Clearside Biomedical, DORC, EyePoint, Genentech/Roche, Kodiak, Notal Vision, Novartis, ONL Therapeutics, PolyPhotonix, Recens Medical, Regeneron, Regenxbio, Santen; Financial support – Adverum, Aerpio, Allergan (an AbbVie company), Apellis, Clearside Biomedical, EyePoint, Genentech/Roche, Neurotech, Novartis, Opthea, Regeneron, Regenxbio, Samsung, Santen; Lecturer – Regeneron A.C.: Consultant – Alcon, Allergan (an AbbVie company), Bayer, Novartis, Roche; Financial support – Bayer and Novartis; Lecturer – Allergan (an AbbVie company), Bayer, Novartis R.K.M.: Consultant – 2nd MD, Alicimed, Eli Lilly, KAEPS, MCIC Vern, Samsung, Santen, System Analytic; Financial support – Allegro, Allergan (an AbbVie company), Bioepis, Boehringer Ingelheim, Genentech, GrayBug, KalVista, Santen. A.J.L.: Advisory board – Allergan (an AbbVie company), Bayer; Financial support – Allergan (an AbbVie company), Bayer; Lecturer – Novartis M.O.: Consultant – Alcon, Allergan (an AbbVie company), Bausch + Lomb, Bayer, Hoya, Novartis, Pfizer, Santen; Financial support – Alcon, Bayer, Novartis, Otsuka, Pfizer, Santen, Senju Sponsored by Allergan plc, Dublin, Ireland (before its acquisition by AbbVie, Inc, North Chicago, Illinois). The sponsor participated in the design of the study, data management, data analysis, interpretation of the data, and preparation, review, and approval of the manuscript. Evidence Scientific Solutions, Inc, Philadelphia, Pennsylvania, prepared a draft of the manuscript under the direction of the authors and provided editorial assistance, funded by AbbVie. All authors met the ICMJE authorship criteria. Neither honoraria nor payments were made for authorship. Obtained funding: N/A
Publisher Copyright:
© 2020 American Academy of Ophthalmology
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). Design: Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. Participants: The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. Methods: At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). Main Outcome Measures: Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). Results: For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was −147 μm, −146 μm, and −142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Conclusions: Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.
AB - Purpose: To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naïve neovascular age-related macular degeneration (nAMD). Design: Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. Participants: The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. Methods: At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). Main Outcome Measures: Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). Results: For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was −147 μm, −146 μm, and −142 μm in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. Conclusions: Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden.
KW - Abicipar
KW - Anti-VEGF
KW - Choroidal neovascularization
KW - DARPin therapeutic
KW - Intravitreal injection
KW - Neovascular age-related macular degeneration
KW - Ranibizumab
KW - Treatment burden
KW - Visual acuity
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U2 - 10.1016/j.ophtha.2020.11.017
DO - 10.1016/j.ophtha.2020.11.017
M3 - Article
C2 - 33221326
AN - SCOPUS:85099612656
VL - 128
SP - 1027
EP - 1038
JO - Ophthalmology
JF - Ophthalmology
SN - 0161-6420
IS - 7
ER -