Author: Peter J. Kertes
Co-authors: Carl Regillo, Peter K. Kaiser, Ramin Tadayoni, Mark Gillies, Iryna Lobach, Siegbert Guenther, Tina Maio-Twofoot, Dsouza D, Frank G. Holz
Abstract
Purpose: To present the 32-week results from TALON, a prospective Phase IIIb superiority study evaluating whether brolucizumab (BRO) 6mg achieved superior treatment interval distribution vs aflibercept (AFL) 2mg with non-inferior visual outcomes using a matched (Treat-and-Extend) treatment regimen in patients with neovascular age-related macular degeneration.Setting/Venue: The TALON (NCT04005352) study was conducted across 118 sites in the following 20 countries: USA, Canada, Argentina, France, UK, Belgium, Netherlands, Germany, Austria, Switzerland, Sweden, Czech Republic, Italy, Spain, Portugal, Israel, Republic of Korea, Australia, Malaysia, and Taiwan.
Methods: TALON is an ongoing, 64-week, two-arm, randomized, double-masked, multicenter study. Treatment-naive patients aged ?50 years, with BCVA between ?83 and ?38 ETDRS letters were included. Patients were randomized 1:1 to either BRO 6mg or AFL 2mg with injections at Weeks (W) 0, 4, 8 and 16 followed by 4-week interval adjustments depending on disease activity (DA) up to an interval of 16 weeks (q16w). At W32, the longest potential interval was q12w. If DA occurred at any visit, the subsequent interval was shortened by 4 weeks to a minimal interval of 4 weeks. After introduction of an urgent safety measure (USM), all patients requiring a q4w interval were discontinued and moved to standard of care. Co-primary endpoints were distribution of the last treatment interval with no DA at W32 and average change in BCVA from baseline to W28 and W32. Key secondary endpoints included proportion of patients with ?15-letter gain from baseline or ?84 letters up to W32, average change from baseline in central subfield thickness (CSFT) and presence of intraretinal fluid
(IRF) and/or subretinal fluid (SRF), and sub-retinal pigment epithelium (RPE) fluid at W28 and W32. Incidence of adverse events (AEs) and ?15-letter loss was also reported.
Results: Co-primary endpoints were met, with BRO achieving superiority to AFL in distribution of last interval with no DA (q12w: 38.5% vs 19.8%; q8w: 35.8% vs 39.9%; q4w: 25.7% vs 40.2% in BRO vs AFL, respectively; P<0.0001) and non-inferiority to AFL for average change in BCVA from baseline at W28 and W32 (BRO +5.2 vs AFL +5.1 letters; difference 0.1 [95% CI: ?1.3, 1.5; P<0.0001]). In the BRO arm, 24% gained ?15 letters up to W32 vs 25% in the AFL arm, respectively. Least square mean difference in average change in CSFT (?m) from baseline at W28 and W32 (BRO ?166.9 vs AFL?140.0) was ?26.9 (95% CI: ?46.3, ?7.5; P=0.007). Fewer BRO vs AFL patients had IRF and/or SRF and sub-RPE fluid. The most common reason for study treatment discontinuation prior to W32 was sponsor request (BRO: 9.0%; AFL: 17.9%), due to the USM. Incidence of ocular AEs, serious ocular AEs and ocular AEs of special interest (AESIs) in the BRO vs AFL arms were 26.5% vs 21.5%, 2.2% vs 0.5%, 5.5% vs 1.1% respectively. In the BRO arm, 1 patient with AESIs lost ?15 letters from baseline at W32 vs 0 in the AFL arm.
Conclusions: The 32-week results from TALON show that more patients treated with BRO achieved a longer treatment interval without DA, alongside non-inferior vision gains, and better anatomical outcomes when compared with AFL, with an overall favorable benefit-risk profile.
