Authors: Geoff Williams, Jeffrey Willis, Zdenka Haskova, David Silverman, Jane Ives, Karen Basu, Hugh Lin.

Author Disclosure Block: G. Williams: Membership on advisory boards or speakers’ bureaus; Name of for-profit or not-for-profit organization(s); Novartis, Bayer, Roche. Membership on advisory boards or speakers’ bureaus; Description of relationship(s); Advisory Boards. Funded grants or clinical trials; Name of for-profit or not-for-profit organization(s); Novartis, Bayer, Roche, Abvie, Chengdu Kanghong Biotech. Funded grants or clinical trials; Description of relationship(s); Clinical Trials. J. Willis: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Genentech. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee. Z. Haskova: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Genentech Inc. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee. D. Silverman: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); F. Hoffmann-La Roche. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee. J. Ives: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); F. Hoffmann-La Roche. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee. K. Karen Basu: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); F. Hoffmann-La Roche. H. Lin: All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Name of for-profit or not-for-profit organization(s); Genentech. All other investments or relationships that could be seen by a reasonable, well-informed participant as having the potential to influence the content of the educational activity; Description of relationship(s); Employee.

Abstract Body:

Purpose: Evidence from Phase 2 study (BOULEVARD), and preclinical models, suggest that dual inhibition of Ang-2 and VEGF-A with faricimab, the first bispecific antibody designed for intraocular use, may synergistically promote vascular stability, leading to improved outcomes beyond intravitreal anti-VEGF monotherapy in patients with DME. The Phase 3 YOSEMITE and RHINE trials are designed to assess the safety, efficacy, and durability of faricimab over aflibercept in DME.
Study Design: YOSEMITE (NCT03622580) and RHINE (NCT03622593) are identical, phase 3, randomized, double-masked, active comparator-controlled trials of faricimab in treatment-naïve and previously anti-VEGF-treated patients with center-involving DME.
Methods: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks (Q8W), following 6 initial Q4W doses; faricimab 6.0 mg administered per personalized treatment interval (PTI), following a minimum of 4 initial Q4W doses; or aflibercept 2.0 mg Q8W, following 5 initial Q4W doses. The PTI algorithm is a protocol-driven regimen based on the treat-and-extend concept, using prespecified BCVA and anatomical criteria measured at active dosing visits to adjust treatment intervals. Noninferiority, followed by superiority in treatment-naïve patients and then the overall population, of the two faricimab arms over aflibercept was assessed hierarchically. The primary efficacy endpoint was the mean change in BCVA from baseline at 1 year (Week 48, 52, and 56 average). Secondary endpoints include proportion of patients with ≥ 2-step ETDRS-DRSS improvement from baseline, proportion of patients gaining ≥15 ETDRS letters, change from baseline in CST, and proportion of patients in the PTI arm on Q4W, Q8W, Q12W, or Q16W treatment intervals, at 1 year. Safety was assessed by incidence and severity of ocular and non-ocular adverse events.
Results: In the Phase 2 BOULEVARD study, faricimab 6.0 mg Q4W resulted in superior vision gains and greater improvements in diabetic retinopathy severity at Week 24, and demonstrated potential for extended durability in a 16-week off-treatment observation period, over ranibizumab Q4W. YOSEMITE and RHINE are ongoing trials. Year-1 results will be presented at the meeting.
Conclusions: YOSEMITE and RHINE evaluate the safety, efficacy, and durability of faricimab in patients with DME using PTI, a protocol-driven regimen based on treat-and-extend, or Q8W dosing. Year-1 results will be presented at the meeting.