Author: Paolo Lanzetta
Co-authors:
Abstract
Purpose:Preclinical experiments have previously shown that a high dose of intravitreal aflibercept (IVT AFL) resulted in prolonged efficacy in a representative model system compared with the equivalent of IVT-AFL 2 mg, the currently indicated dose. The phase 2 CANDELA trial assessed the safety and efficacy of IVT-AFL 8 mg versus IVT-AFL 2 mg in patients with neovascular age-related macular degeneration (nAMD).
Setting/Venue:
CANDELA was a phase 2, randomized, single-masked, open-label, 44-week clinical trial (NCT04126317) that was conducted across 46 sites in the United States between November 2019 and November 2021.
Methods:
Treatment-naïve patients (≥50 years old) with active subfoveal choroidal neovascularization secondary to nAMD and a best corrected visual acuity (BCVA) of 78 to 24 letters (approximately 20/32 to 20/320) in the study eye were enrolled. A total of 106 patients were randomized 1:1 to receive 3 monthly doses of either IVT-AFL 8 mg (n=53) or IVT-AFL 2 mg (n=53) followed by doses at Weeks 20 and 32. The primary endpoints were safety and the proportion of eyes without retinal fluid in the center subfield at Week 16.
Results:
Overall, a greater proportion of patients were female (62.3%); the mean (standard deviation [SD]) age was 77.4 (8.0) years and mean (SD) baseline BCVA was 58.0 (12.1) letters. The incidence of ocular adverse events (AEs) through Week 44 was 37.7% (20/53) for the IVT-AFL 8 mg group and 37.7% (20/53) for the IVT-AFL 2 mg group. No new safety signals were identified; no serious events of intraocular inflammation, nor events of occlusive vasculitis or anti-platelet trialists' collaboration (APTC)-defined arterial thromboembolic were reported through Week 44. The proportion of eyes with no retinal fluid in the center subfield was 50.9% (27/53) for the IVT-AFL 8 mg group and 34.0% (18/53) for the IVT-AFL 2 mg group (treatment difference, 17.0% [95% CI, −1.6%, 35.5%]; P=0.0770) at Week 16 and 39.6% (21/53) and 28.3% (15/53), respectively (treatment difference, 11.3% [95% CI, –6.6%, 29.2%]; nominal P=0.2185) at Week 44. Eyes in the IVT-AFL 8 mg versus IVT-AFL 2 mg group showed a greater reduction from baseline in median central subfield thickness (−162 µm vs −88 µm), and a numerically higher increase from baseline in mean BCVA (+7.9 vs +5.1 letters; nominal P=0.1957) at Week 44.
Conclusions:
The overall safety of IVT-AFL 8 mg was similar to that of IVT-AFL 2 mg. In this study, we observed anatomic and functional improvements with IVT-AFL 8 mg, suggesting potential additional therapeutic benefit in comparison to IVT-AFL 2 mg in patients with nAMD.
Financial disclosures:
Paolo Lanzetta: Consultant for Aerie, Allergan, Apellis, Bayer, Biogen, Centervue, Novartis, Outlook Therapeutics, and Roche
Funding:
The CANDELA study was funded by Regeneron Pharmaceuticals, Inc. (Tarrytown, NY, USA). The sponsor participated in the design and conduct of the study, analysis of the data, and preparation of this abstract. Medical writing support, under the direction of the author, was provided by ApotheCom and supported by Bayer Consumer Care AG, Basel, Switzerland, in accordance with Good Publication Practice (Ann Intern Med. 2015;163:461–464)