TALON Phase IIIb Study: 32-Week Primary Results of Brolucizumab Using Treat and Extend for Neovascular Age-Related Macular Degeneration.

OBJECTIVE

To compare the efficacy and safety of brolucizumab 6 mg and aflibercept 2 mg using an identical 4-week adjustment treat-and-extend regimen in patients with neovascular age-related macular degeneration (nAMD).

DESIGN

Randomized, double-masked, multicenter, active-controlled, 2-arm, phase IIIb study.

PARTICIPANTS

Patients (N = 737) with untreated, active choroidal neovascularization secondary to nAMD.

METHODS

Patients were randomized 1:1 to either brolucizumab 6 mg or aflibercept 2 mg with injections at weeks 0, 4, 8, and 16 followed by 4-week interval adjustments depending on disease activity (DA) up to intervals of 16 weeks. After the introduction of the urgent safety measure, patients requiring a 4-week interval were discontinued from study treatment and moved to the standard of care.

MAIN OUTCOME MEASURES

Coprimary end points were the distribution of the last treatment interval with no DA at week 32 and the average change in best-corrected visual acuity (BCVA) from baseline to weeks 28 and 32. Key secondary end points included average change from baseline in central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), and subretinal pigment epithelium fluid at weeks 28 and 32. Safety end points included the incidence of ocular and nonocular adverse events (AEs) and AEs of special interest (AESIs).

RESULTS

Brolucizumab achieved superiority to aflibercept in the distribution of last interval with no DA at week 32 (proportion of patients on 12-week treatment intervals: 38.5% vs. 19.8%; 8 weeks: 35.8% vs. 39.9%; 4 weeks: 25.7% vs. 40.2%, respectively; P < 0.0001) and noninferiority to aflibercept for least square mean difference in average change in BCVA from baseline at weeks 28 and 32 (+5.2 vs. +5.1; P < 0.0001). The least square mean difference in the average change in CSFT (μm) from baseline at weeks 28 and 32 (brolucizumab -172.8 vs. aflibercept -142.5) was -30.3 (P = 0.002). Fewer brolucizumab versus aflibercept patients had IRF and/or SRF and subretinal pigment epithelium fluid. Incidences of ocular AEs, serious ocular AEs, and AESIs in the brolucizumab versus aflibercept arms were 29.2% versus 26.1%, 2.5% versus 0.5%, and 5.5% versus 1.1%, respectively.

CONCLUSIONS

In TALON, more brolucizumab-treated patients achieved longer treatment intervals without DA than aflibercept with comparable visual gains. Brolucizumab showed improved anatomical outcomes and demonstrated an overall favorable benefit/risk profile.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.