Skip to main page content

Exploring Ang-2 signalling in vascular stability in patients with DME receiving faricimab in phase 2 and phase 3 trials

Theme:
Retina
What:
Paper Presentation | Présentation d'article
When:
2:05 PM, Saturday 11 Jun 2022 (7 minutes)
How:

Authors: Varun Chaudhary, Anat Loewenstein, Veeral Sheth, Karl Csaky, Rose Edmonds, Michael Chang, Jeffrey R. Willis, Zdenka Haskova, Peter D. Westenskow. 
Author Disclosure Block: V. Chaudhary: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Novartis, Bayer. Any direct financial payments including receipt of honoraria; Description of relationship(s); Speaker fees. Membership on advisory boards or speakers’ bureaus; Name of for-profit or not-for-profit organization(s); Novartis, Bayer, Roche, Alcon Inc.. Membership on advisory boards or speakers’ bureaus; Description of relationship(s); Advisory board. Funded grants or clinical trials; Name of for-profit or not-for-profit organization(s); Novartis, Bayer. Funded grants or clinical trials; Description of relationship(s); Grants and clinical trials. A. Loewenstein: Membership on advisory boards or speakers’ bureaus; Name of for-profit or not-for-profit organization(s); Allergan, Bayer, BeyeOnics, ForSight Labs, NotalVision, Novartis and Roche. Membership on advisory boards or speakers’ bureaus; Description of relationship(s); Consultant. V. Sheth: Membership on advisory boards or speakers’ bureaus; Name of for-profit or not-for-profit organization(s); Genentech, Inc., Alimera, EyePoint, Genentech, Inc., Novartis. Membership on advisory boards or speakers’ bureaus; Description of relationship(s); Speaker, Consultant. Funded grants or clinical trials; Name of for-profit or not-for-profit organization(s); Allergan, Alimera Sciences, DRCR, Genentech, Inc., Ionis, Novartis, Regeneron, Santen, SamChungDang, IvericBio, Gyroscope, Chengdu Kanghong, SalutarisMD, NGM Biopharmaceuticals. Funded grants or clinical trials; Description of relationship(s); Contracted research. K. Csaky: Membership on advisory boards or speakers’ bureaus; Name of for-profit or not-for-profit organization(s); Acucela, Allergan, Applied Genetic Technologies Corporation, Astellas, Gyroscope, Heidelberg, Novartis, Ocular Therapeutix, Regeneron, Ribomics, Roche/Genentech, Inc.. Membership on advisory boards or speakers’ bureaus; Description of relationship(s); Consultant. R. Edmonds: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Genentech, Inc.. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee. M. Chang: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Genentech, Inc.. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee. J.R. Willis: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Genentech, Inc.. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee. Z. Haskova: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Genentech, Inc.. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee. P.D. Westenskow: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); F. Hoffmann-La Roche Ltd.. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee.

Purpose: Faricimab, a bispecific antibody, targets both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), which are key drivers of vascular instability. The purpose of these analyses is to explore the impact of dual inhibition of Ang-2 and VEGF-A by faricimab on vascular stability. 

Study Design: BOULEVARD (NCT02699450) was a phase 2, prospective, multicentre clinical trial. YOSEMITE (NCT03622580) and RHINE (NCT03622593) are two identical phase 3, randomised, double-masked, active comparator-controlled, multicentre clinical trials in DME, currently ongoing. Preclinical studies were performed in a mouse model of spontaneous choroidal neovascularisation (CNV). 

Methods: In BOULEVARD, patients were randomized to intravitreal ranibizumab 0.3 mg, faricimab 1.5 mg or faricimab 6.0 mg, administered every 4W for 20W, followed by a 16W observation period to assess durability. In a post hoc analysis, sustained retinal stability to W24 was assessed. Vascular stability was also assessed in the phase 3 trials. In preclinical experiments, JR5558 mice were treated with antibodies against Ang-2, VEGF-A or both (bispecific antibody [VA2]). Untreated and immunoglobulin G (IgG)-treated mice were used as controls. Vascular stability was evaluated at baseline and 1W (PT1), 3W (PT2) and 5W (PT3) post treatment. 

Results: In a post hoc analysis of BOULEVARD, > 50% of patients achieved retinal stability through W24. Phase 3 vascular stability data will be presented. In preclinical experiments, significant reduction of CNV leakage (P<0.05 to P<0.001) was observed in JR5558 mice treated with Ang-2, VEGF-A or VA2 versus controls at PT1. Treatment with VA2 antibody significantly reduced Iba1+ cell infiltration versus IgG control at PT1/PT2 (P<0.05) and CD45+ CD11b+ cell infiltration versus untreated control at PT1 (P<0.05). At PT3, only anti-Ang-2- and VA2-treated mice showed significant reduction in number of Iba1+ macrophages (P<0.0001) versus IgG control. There was significant reduction in fibronectin+ area with VA2 (P<0.01) and anti-Ang-2 (P<0.001) versus IgG at PT1, not with anti-VEGF-A alone. This was maintained only with VA2 at PT2 (P<0.01) and PT3 (P<0.05). 

Conclusions: These data support the involvement of Ang-2 signalling in vascular stability in patients with DME.

Speaker
Scientific Planning Committee Chair - Co-Developed Symposium
Session detail
Allows attendees to send short textual feedback to the organizer for a session. This is only sent to the organizer and not the speakers.
To respect data privacy rules, this option only displays profiles of attendees who have chosen to share their profile information publicly.

Changes here will affect all session detail pages