Brolucizumab: a novel anti-VEGF humanized single-chain antibody fragment for treating w-AMD

ABSTRACT

Introduction

Wet age-related macular degeneration (w-AMD) represents the leading cause of visual impairment in the elderly in the developed countries. Intravitreal antivascular endothelial growth factor (VEGF) drugs are currently considered as the first-line treatment option for treating w-AMD; however, the frequent injection intervals have lit the way to investigate novel anti-VEGF agents allowing a more extended treatment regimen. Brolucizumab is a single-chain antibody fragment targeting all the isoforms of VEGF-A. Phase III HAWK and HARRIER trials have shown a longer durability and superior anatomical outcomes as compared with the standard of care by adopting a quarterly regimen for treating w-AMD. Brolucizumab has been approved in Europe, USA, and Japan for the management of w-AMD.

Areas covered

This article presents an overview of w-AMD and investigates the progress of brolucizumab through clinical trials. It offers insights into where brolucizumab may be placed in the current market of anti-VEGF agents and its potential advantages over the previous molecules adopted for treating w-AMD.

Expert Opinion

The possibility of administering brolucizumab with more dilated treatment intervals represents an important advantage to decrease the treatment burden and improve patient compliance. Brolucizumab represents a possible drug switching option in non-responding patients to other anti-VEGF drugs.

KEYWORDS:

• Brolucizumab
• macular degeneration
• anti-VEGF
• novel anti-VEGF agent
• HAWK
• HARRIER

Article highlights

• Brolucizumab is a humanized, single-chain antibody fragment (scFv) composed of 255 amino-acids, which inhibits all the isoforms of VEGF-A.

• On the basis of its high solubility and concentration properties, brolucizumab can be delivered with a binding capacity greater than 11 or 22 times than other anti-VEGF agents

• Results from multicenter, phase III HAWK and HARRIER trials showed that brolucizumab administered with a quarterly regimen had a non-inferior efficacy profile as compared with aflibercept, revealing also superior anatomical outcomes for the former.

• Some safety concerns were raised regarding the presence of severe ocular AEs in HAWK and HARRIER, including episodes of intraocular inflammation, vasculitis and occlusion (RAO); however, post hoc studies revealed that these AEs occurred in a small percentage of patients treated with brolucizumab (around 2%)

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.