Authors: Raman Tuli, 1.Carlos Quezada Ruiz, 2.David Silverman, 3.Vaibhavi Patel, 4.Karen Basu, 5.Hugh Lin.

Author Disclosure Block: R. Tuli: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Hoffman Laroche Ltd. Any direct financial payments including receipt of honoraria; Description of relationship(s); Consultant. Funded grants or clinical trials; Name of for-profit or not-for-profit organization(s); Hoffman Laroche, Novartis, Aplellis. Funded grants or clinical trials; Description of relationship(s); PI for the following Clinical Trials, TENAYA,KESTRAL, RAPTOR, RAVEN, DERBY. 1. Quezada Ruiz: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Genentech. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee. 2. Silverman: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Hoffmann La Roche. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee. 3. Patel: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Hoffmann La Roche. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee. 4. Basu: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Genentech. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee. 5. Lin: Any direct financial payments including receipt of honoraria; Name of for-profit or not-for-profit organization(s); Genentech. Any direct financial payments including receipt of honoraria; Description of relationship(s); Employee.

Abstract Body:

Purpose: Dual inhibition of angiopoietin-2 and vascular endothelial growth factor (VEGF)-A with faricimab, the first bispecific antibody designed for intraocular use, may promote vascular stability with sustained efficacy and extended durability in patients with neovascular age-related macular degeneration (nAMD). The phase 3 TENAYA and LUCERNE trials compare the safety, efficacy, and durability of faricimab with intravitreal anti-VEGF monotherapy in patients with nAMD.
Study Design: TENAYA (NCT03823287) and LUCERNE (NCT03823300) are identical, phase 3, randomized, double-masked, active comparator-controlled, 112-week studies of faricimab in nAMD.
Methods: Treatment-naïve patients were randomized 1:1 to faricimab 6.0 mg up to every 16 weeks (Q16W) or aflibercept 2.0 mg Q8W. The faricimab arm received 4 initial Q4W doses to Week 12, and were assessed for protocol-defined disease activity at Weeks 20 and 24. Patients with no evidence of active disease at Weeks 20 or 24 received Q16W dosing through Week 60; those with active disease at Week 20 switched to Q8W dosing; patients with first signs of active disease at Week 24 switched to Q12W dosing. From Week 60, faricimab-treated patients follow a personalized treatment interval based on a protocol-driven treat-and-extend regimen through Week 108. Patients randomized to aflibercept received 3 initial Q4W doses to Week 8, then fixed Q8W dosing through Week 108. Efficacy and safety outcomes were assessed at Q4W study visits through Week 112. The primary efficacy endpoint is the mean change in best-corrected visual acuity from baseline averaged over Weeks 40, 44, and 48. Secondary endpoints include the proportion of patients receiving faricimab Q16W, Q12W, and Q8W; and changes in anatomic outcomes on OCT. Safety outcomes include the incidence and severity of ocular and nonocular adverse events.
Results: In phase 2 studies, faricimab Q4W or Q8W were associated with robust vision and anatomic improvements that were comparable to ranibizumab Q4W (AVENUE), and faricimab Q12W or Q16W demonstrated sustained efficacy and durability over 1 year (STAIRWAY). TENAYA and LUCERNE are ongoing trials; Year 1 study results will be available and presented at the meeting.
Conclusions: TENAYA and LUCERNE evaluate the safety, efficacy, and durability of an extended (up to Q16W) dosing regimen for intravitreal faricimab in patients with nAMD.