Author: Ian Pearce (United Kingdom)
Co-authors: Glenn J. Jaffe, Bianca Gerendas, Kemal Asik, Stefan Scheidl, Francis Abreu, David Silverman
Faricimab is a novel bispecific antibody designed to inhibit angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF)-A. Dual Ang-2/VEGF-A inhibition promotes enhanced vascular stability, which can translate to anatomic and durability benefits beyond that achievable with VEGF-A inhibition alone. Here, we present a visualisation of the faricimab PTI dosing dynamics, illustrated with profiles of patients with DME from the phase 3 YOSEMITE/RHINE trials. Faricimab PTI dosing aimed to tailor treatment intervals per individual patient needs to improve and maintain vision gains, while reducing treatment burden. Durability of faricimab effect in the PTI arm was a key objective of YOSEMITE/RHINE.
YOSEMITE (NCT03622580) and RHINE (NCT03622593) are identical, randomised, double-masked, active comparator–controlled, 100-week, phase 3 trials of faricimab in patients with DME. Eyes were randomised (1:1:1) into 3 arms: faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg PTI or the control arm, aflibercept 2.0 mg Q8W.
The PTI algorithm is a protocol-driven regimen based on the treat-and-extend concept, with dosing intervals adjusted in 4-week increments (up to Q16W) using prespecified central subfield thickness (CST) and best-corrected visual acuity (BCVA) criteria. Treatment intervals could be extended after week 12 if a reference CST value below the threshold of 325 μm was achieved. Thereafter, dosing interval decisions by automated interactive voice/web response system (IxRS) were based on change in CST from this reference value, with intervals extended by 4 weeks, reduced by 4 or 8 weeks or maintained based on both CST assessed by masked harmonised central reading centre graders and BCVA assessed by masked study site assessors. Only CST and BCVA at treatment visits, not sham visits, were considered by the IxRS. To maintain masking, eyes received sham injections at study visits when not receiving treatment. Additional anatomical endpoints were evaluated using optical coherence tomography (OCT), colour fundus photography and fundus fluorescein angiography, with optional OCT angiography. Achievement of extended treatment intervals was assessed at week 52.
Overall, 1891 patients were enrolled in YOSEMITE and RHINE (N = 940 and 951, respectively). Among patients assigned to the faricimab PTI arm, greater than 70% achieved ≥ Q12W treatment intervals and greater than 50% achieved the Q16W treatment interval at week 52, whereas 12% and 16% of patients were on the Q4W and Q8W treatment intervals, respectively, at week 52. Here, we present a post hoc analysis of the overall dynamics of faricimab PTI dosing from baseline up to week 52. Specifically, representative cases will be described and associated retinal images presented for the following PTI scenarios: (A) CST threshold met at week 12 and rapid, immediate extension to Q16W by week 32; (B) criteria for extension met at a later timepoint, with Q16W interval reached more slowly; and (C) scenario where patients fluctuate between extended and more frequent treatment intervals throughout the first year.
This post hoc analysis of individualised treatment frequency dynamics illustrates how the faricimab PTI algorithm was used effectively to optimise treatment intervals according to the heterogeneous needs of patients with DME. The PTI faricimab arm demonstrated strong durability of faricimab effect, with 52% of patients on the Q16W treatment interval and 72% of patients on the Q12W or Q16W treatment intervals at week 52.
Ian Pearce: (Consultant) Alimera, Apellis, Allergan, Bayer, Biogen, Novartis, Roche; (Lecture fees) Apellis, Allergan, Bayer, Biogen, Novartis, Roche. Glenn J. Jaffe:(Consultant) EyePoint, Gemini, Iveric, Novartis, Roche/Genentech. Bianca Gerendas: (Consultant) Roche, Novartis; (Research support) Digital Diagnostics. Kemal Asik: (Employment) Genentech, Inc. Stefan Scheidl: (Employment) F. Hoffmann-La Roche Ltd. Francis Abreu: (Employment) Genentech, Inc. David Silverman: (Employment) Roche Products Ltd. Zdenka Haskova: (Employment) Genentech, Inc.
Please add below extra co-author: Co-author 7 first name: Zdenka Co-author 7 last name: Haskova Co-author 7 affiliation: Genentech, Inc., South San Francisco, CA