Faricimab Treat-and-Extend for Diabetic Macular Edema

Purpose: To evaluate the 2-year efficacy, durability, and safety of dual angiopoietin-2 and vascular endothelial growth factor (VEGF) A pathway inhibition with intravitreal faricimab according to a personalized treat-andextend (T&E)-based regimen with up to every-16-week dosing in the YOSEMITE and RHINE (ClinicalTrials.govidentifiers, NCT03622580 and NCT03622593, respectively) phase 3 trials of diabetic macular edema (DME).Design: Randomized, double-masked, noninferiority phase 3 trials.Participants: Adults with visual acuity loss (best-corrected visual acuity [BCVA] of 25e73 letters) due tocenter-involving DME.Methods: Patients were randomized 1:1:1 to faricimab 6.0 mg every 8 weeks, faricimab 6.0 mg T&E (previously referred to as personalized treatment interval), or aflibercept 2.0 mg every 8 weeks. The T&E up to every16-week dosing regimen was based on central subfield thickness (CST) and BCVA change.Main Outcome Measures: Included changes from baseline in BCVA and CST, number of injections,durability, absence of fluid, and safety through week 100.Results: In YOSEMITE and RHINE (n ¼ 940 and 951, respectively), noninferior year 1 visual acuity gains weremaintained through year 2; mean BCVA change from baseline at 2 years (weeks 92, 96, and 100 average) with faricimabevery 8 weeks (YOSEMITE and RHINE, þ10.7 letters and þ10.9 letters, respectively) or T&E (þ10.7 letters and þ10.1letters, respectively) were comparable with aflibercept every 8 weeks (þ11.4 letters and þ9.4 letters, respectively). Themedian number of study drug injections was lower with faricimab T&E (YOSEMITE and RHINE, 10 and 11 injections,respectively) versus faricimab every 8 weeks (15 injections) and aflibercept every 8 weeks (14 injections) across bothtrials during the entire study. In the faricimab T&E arms, durability was improved further during year 2, with > 60% ofpatients receiving every-16-week dosing and approximately 80% receiving every-12-week or longer dosing at week 96.Almost 80% of patients who achieved every-16-week dosing at week 52 maintained every-16-week dosing without aninterval reduction through week 96. Mean CST reductions were greater (YOSEMITE/RHINE weeks 92/96/100 average:faricimab every 8 weeks e216.0/e202.6 mm, faricimab T&E e204.5/e197.1 mm, aflibercept every 8 weeks e196.3/e185.6 mm), and more patients achieved absence of DME (CST < 325 mm; YOSEMITE/RHINE weeks 92e100: faricimab every 8 weeks 87%e92%/88%e93%, faricimab T&E 78%e86%/85%e88%, aflibercept every 8 weeks 77%e81%/80%e84%) and absence of intraretinal fluid (YOSEMITE/RHINE weeks 92e100: faricimab every 8 weeks 59%e63%/56%e62%, faricimab T&E 43%e48%/45%e52%, aflibercept every 8 weeks 33%e38%/39%e45%) with faricimab every 8 weeks or T&E versus aflibercept every 8 weeks through year 2. Overall, faricimab was well tolerated, witha safety profile comparable with that of aflibercept.Conclusions: Clinically meaningful visual acuity gains from baseline, anatomic improvements, and extendeddurability with intravitreal faricimab up to every 16 weeks were maintained through year 2. Faricimab given as apersonalized T&E-based dosing regimen supports the role of dual angiopoietin-2 and VEGF-A inhibition topromote vascular stability and to provide durable efficacy for patients with DME