Lucy Cobbs, MD
Wills Eye Hospital
Dr. Carl Regillo from Wills Eye Hospital / Mid-Atlantic Retina presented the 32-week primary outcomes of the Phase IIIb TALON study for the first time. The study analyzed the efficacy and safety of brolucizumab versus aflibercept in a matched treat-and-extend regimen in patients with neovascular age-related macular degeneration (nAMD).
TALON was a large global, sixty-four-week prospective randomized double-masked superiority study with two main objectives. First, the study evaluated whether brolucizumab is superior to aflibercept in extending duration of the treatment intervals. The corresponding endpoint to evaluate this was the distribution of the last treatment interval with no disease activity up to week 32. TALON’s second objective was assessing noninferior visual outcome of brolucizumab relative to aflibercept, with the endpoint of mean change in best-corrected visual acuity (BCVA) from baseline at weeks 28 and 32.
In terms of study design, TALON was a 1:1 two-armed study of brolucizumab 6mg and aflibercept 2mg. The initiation phase was comprised of both drugs dosed monthly for 3 doses followed by an 8-week dose. This was then followed by 4-week extensions up to week 16 if there was no disease activity. True to clinical practice, investigators were instructed to treat to maintain a dry macula if possible.
The study included patients with treatment-naïve nAMD and a Snellen visual acuity equivalent of 20/25 to 20/200. Later in the course of the study, once the MERLIN safety study results were known, the study was amended to discontinue patients needing every 4-week injections after the initiation phase, and thereafter, the treat and extend range was 8-16 weeks up to week 64.
Baseline demographics and ocular characteristics of the study populations were well-balanced between the two treatment groups and typical of treatment-naïve nAMD patients.
Brolucizumab met both primary end points. Brolucizumab was found to be superior to aflibercept in the distribution of the last treatment interval and noninferior in visual outcome. Additionally, brolucizumab achieved greater reduction in central subfield thickness from baseline at weeks 28 and 32 compared to aflibercept.
There were imbalances in safety profiles between the two drugs, comparable to previously reported data. Adverse events of special interest, including retinal vascular occlusion, endophthalmitis, and intraocular inflammation, disproportionately affected brolucizumab patients compared to aflibercept patients.
Dr. Regillo concluded his presentation noting that the 64-week end of study results will be available later this year and may help elucidate how these drugs can be extended over time.