An assessment of the impact of disease activity criteria on dosing interval assignment in clinical trial patients with nAMD

Abstract

Purpose : Clinical treatment decisions for patients with neovascular age-related macular degeneration (nAMD) are based on disease activity. Likewise, in clinical trials, disease activity criteria guide dosing regimen allocation and dosing interval adjustment. Criteria may differ between trials, complicating comparison of durability outcomes. Faricimab (Vabysmo) (FAR), a dual angiopoietin-2/vascular endothelial growth factor-A inhibitor, maintained vision, with extended treatment durability and fewer injections vs aflibercept through 2 years in the TENAYA/LUCERNE (NCT03823287/NCT03823300) nAMD trials. This analysis evaluated how applying different disease activity criteria may have impacted FAR dosing interval assignment in TENAYA/LUCERNE.

Methods : In TENAYA/LUCERNE, patients (N=1329) were randomized 1:1 to FAR 6.0 mg or aflibercept Q8W. In the FAR arm, patients were assigned to treatment intervals up to every 16 weeks (Q16W; n=665) based on protocol-defined disease activity designed to reflect clinical practice, defined as: best-corrected visual acuity (BCVA) loss of ≥5 (vs mean over 2 previous visits) or ≥10 letters (vs highest BCVA over 2 previous visits); or central subfield thickness (CST) >50 µm (vs mean over 2 previous visits) or ≥75 µm (vs lowest CST over 2 previous visits); or new macular hemorrhage. Application of these criteria at week 20 was compared with application of vision and anatomic disease criteria (adapted from dose regimen modification criteria used in PULSAR; NCT04423718) at week 20, defined as: BCVA loss >5 letters (vs week 16 BCVA) and CST increase >25 µm (vs week 16 CST) or new macular hemorrhage.

Results : When disease activity was based on vision or anatomic criteria (TENAYA/LUCERNE), 78% of FAR patients were assigned to ≥Q12W dosing at week 20 (Fig 1). In contrast, in a hypothetical scenario where disease activity was based on vision and anatomic criteria, 96% of FAR patients would have been assigned to ≥Q12W dosing at week 20 (Fig 1).

Conclusions : Application of disease activity criteria in clinical trials can have a significant impact on dosing interval adjustment/determination. Attention should be paid to which criteria best reflect real-world practice to understand the likelihood of trial results translating to treatment burden reductions.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.