Author: Gemmy Cheung
Co-authors: Robyn H. Guymer, Anna-Maria Demetriades, Philippe Margaron, Carlos Quezada Ruiz, David Silverman, Jane Ives, Karen Basu, Audrey Souverain, Ming Yang, Hugh Lin
Abstract
Purpose:Dual inhibition of Ang-2 and VEGF-A with faricimab, a bispecific antibody designed for intraocular use, may promote vascular stability and durable efficacy in patients with nAMD. Here we report pooled efficacy, safety, and durability results through week 48 from the phase 3 TENAYA (NCT03823287)/LUCERNE (NCT03823300) trials and compare anatomical outcomes of faricimab with aflibercept through week 12, after 3 initial doses, in patients with nAMD.
Setting/Venue:
TENAYA and LUCERNE were identical, randomised, double-masked, active comparator–controlled, 112-week, phase 3 trials of faricimab in nAMD.
Methods:
Treatment-naïve patients (pooled N = 1329) were randomized 1:1 to faricimab 6.0 mg up to every 16 weeks (Q16W; n = 665) or aflibercept Q8W (n = 664). After 4 initial doses Q4W, faricimab-treated patients were treated Q8W, Q12W, or Q16W based on protocol-defined disease activity assessments at weeks 20 and 24. Aflibercept-treated patients received 3 initial Q4W doses and then Q8W dosing. Primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) averaged over weeks 40, 44, and 48. Secondary efficacy endpoints, including visual/anatomical outcomes and safety, were assessed Q4W through week 48.
Results:
Faricimab resulted in comparable visual acuity and anatomical outcomes compared with aflibercept averaged over weeks 40, 44, and 48, with 45.3% of faricimab-treated patients on Q16W dosing and 78.7% on ≥ Q12W dosing. When both study treatments were administered Q4W through week 12, mean change in BCVA from baseline was comparable with faricimab versus aflibercept. Faricimab resulted in a greater reduction in mean (95% CI) change in central subfield thickness from baseline through week 12 compared with aflibercept (–145. 4 µm [–149.1, –141.8] vs –132.9 µm [–136.6, –129.2] at week 12, respectively). Proportions of patients with no subretinal fluid (SRF) and no retinal fluid (SRF or intraretinal fluid [IRF]) were greater with faricimab through week 12. Faricimab was well tolerated through week 48, with low rates of intraocular inflammation and no vasculitis or occlusive retinitis events reported.
Conclusions:
TENAYA/LUCERNE data demonstrate that through week 48, faricimab up to Q16W offered durable vision gains/meaningful anatomical improvements that were comparable with aflibercept Q8W and was well tolerated. When treated Q4W through week 12, faricimab resulted in a more rapid improvement in anatomical outcomes compared with aflibercept.
Financial Disclosure:
1.Gemmy Cheung, MBBS, FRCOphth, FAMS, MCI; Financial disclosures: Consultant: Bayer, Novartis, Roche, Allergan, Topcon, Samsung, Behringer-Ingelheim; Research: Bayer, Novartis, Roche, Topcon; Financial Support: Roche, Zeiss
2.Robyn H Guymer, AM, MBBS, PhD, FRANZCO, FAHMS; Financial Disclosures: Consultant: Apellis, Bayer, Novartis, F. Hoffmann-La Roche Ltd. Genentech Inc
3.Anna-Maria Demetriades, MD, PhD; Financial Disclosures: Employee of Genentech, Inc.
4.Philippe Margaron, PhD; Financial Disclosures: Employee of Roche Products Ltd.
5.Carlos Quezada Ruiz, MD; Financial Disclosures: Employee of Genentech, Inc.
6.David Silverman, MBChB; Financial Disclosures: Employee of Roche Products Ltd.
7.Jane Ives, MSc; Financial Disclosures: Employee of Roche Products Ltd.
8.Karen Basu, PhD; Financial Disclosures: Employee of Roche Products Ltd.
9.Audrey Souverain, PharmD, MSc; Financial Disclosures: Employee of F. Hoffmann-La Roche Ltd.
10.Ming Yang, PhD; Financial Disclosures: Employee of Genentech, Inc.
11.Hugh Lin, MD; Financial Disclosures: Employee of Genentech, Inc.