Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes.

Autor: Agostini H; Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Abreu F; Genentech, Inc., South San Francisco, CA, USA., Baumal CR; Tufts Medicine New England Eye Center, Boston, MA, USA.; Apellis Pharmaceuticals, Waltham, MA, USA., Chang DS; Genentech, Inc., South San Francisco, CA, USA., G Csaky K; Retina Foundation of the Southwest, Dallas, TX, USA., Demetriades AM; Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA., Kodjikian L; Department of Ophthalmology, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France.; CNRS UMR 5510 Mateis, INSA, University of Lyon I, Villeurbanne, France., Lim JI; Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, University of Illinois at Chicago, Chicago, IL, USA., Margaron P; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Monés JM; Centro Médico Teknon, Institut de La Màcula and Barcelona Macula Foundation, Barcelona, Spain., Peto T; Centre for Public Health, Queen's University Belfast, Belfast, UK., Ricci F; Department of Experimental Medicine, University 'Tor Vergata', Rome, Italy., Rüth M; F. Hoffmann-La Roche Ltd., Basel, Switzerland., Singh RP; Cleveland Clinic Florida, Stuart, FL, USA., Stoilov I; Genentech, Inc., South San Francisco, CA, USA., Swaminathan B; F. Hoffmann-La Roche Ltd., Mississauga, ON, Canada., Willis JR; Genentech, Inc., South San Francisco, CA, USA., Westenskow PD; F. Hoffmann-La Roche Ltd., Basel, Switzerland. peter.westenskow@roche.com.
Jazyk: angličtina
Zdroj: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie [Graefes Arch Clin Exp Ophthalmol] 2024 Jun 07. Date of Electronic Publication: 2024 Jun 07.
DOI: 10.1007/s00417-024-06531-9
Abstrakt: Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); however, vision gains and anatomical improvements are not sustained over longer periods of treatment, suggesting other relevant targets may be needed to optimize treatments. Additionally, frequent intravitreal injections can prove a burden for patients and caregivers. Angiopoietin-2 (Ang-2) has been explored as an additional therapeutic target, due to the involvement of Ang-2 in DME and nAMD pathogenesis. Recent evidence supports the hypothesis that targeting both VEGF and Ang-2 may improve clinical outcomes in DME and nAMD compared with targeting VEGF alone by enhancing vascular stability, resulting in reduced macular leakage, prevention of neovascularization, and diminished inflammation. Faricimab, a novel bispecific antibody that targets VEGF-A and Ang-2, has been evaluated in clinical trials for DME (YOSEMITE/RHINE) and nAMD (TENAYA/LUCERNE). These trials evaluated faricimab against the anti-VEGFA/B and anti-placental growth factor fusion protein aflibercept, both administered by intravitreal injection. In addition to faricimab efficacy, safety, and pharmacokinetics, durability was evaluated during the trials using a treat-and-extend regimen. At 1 year, faricimab demonstrated non-inferior vision gains versus aflibercept across YOSEMITE/RHINE and TENAYA/LUCERNE. In YOSEMITE/RHINE, faricimab improved anatomic parameters versus aflibercept. Reduction of central subfield thickness (CST), and absence of both DME and intraretinal fluid were greater in faricimab- versus aflibercept-treated eyes. In TENAYA/LUCERNE, CST reductions were greater for faricimab than aflibercept at the end of the head-to-head phase (0-12 weeks), and were comparable with aflibercept at year 1, but with less frequent dosing. CST and vision gains were maintained during year 2 of both YOSEMITE/RHINE and TENAYA/LUCERNE. These findings suggest that dual Ang-2/VEGF-A pathway inhibition may result in greater disease control versus anti-VEGF alone, potentially addressing the unmet needs and reducing treatment burden, and improving real-world outcomes and compliance in retinal vascular diseases. Long-term extension studies (RHONE-X, AVONELLE-X) are ongoing. Current evidence suggests that dual inhibition with faricimab heralds the beginning of multitargeted treatment strategies inhibiting multiple, independent components of retinal pathology, with faricimab providing opportunities to reduce treatment burden and improve outcomes compared with anti-VEGF monotherapy.
(© 2024. The Author(s).)
Databáze: MEDLINE
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