Abicipar pegol for neovascular age-related macular degeneration

ABSTRACT

Introduction

The development of intravitreal anti-vascular endothelial growth factor (VEGF) therapy has revolutionized management of neovascular age-related macular degeneration (nAMD) and serves as the standard of care for treating this chronic, progressive disease. One shortcoming is the need for frequent intravitreal injections to maintain visual gains, which has led to pursuit of long-acting agents to reduce treatment burden.

Areas covered

A literature search was conducted using the keywords ‘abicipar pegol’ and ‘DARPin’ on PubMed.

Expert opinion

DARPin (Designed Ankyrin Repeat Proteins) molecules such as abicipar pegol offer potential therapeutic advantages over antibodies or antibody fragments, including high affinity, stability, and high molar concentration. The phase III SEQUOIA and CEDAR clinical trials suggest that abicipar allows >90% of patients to maintain stable vision with 12-week dosing intervals, comparable to results achieved with monthly ranibizumab injections. Relative to other anti-VEGF agents, intraocular inflammation has been noted in a concerning percentage of patients, which is hypothesized to be related to the manufacturing process rather than the drug itself. Modifications to reduce pro-inflammatory components resulted in reduced inflammation (8.9%) in the MAPLE study. If this high inflammation rate can be further reduced, abicipar has the potential to decrease treatment burden for nAMD patients.

KEYWORDS:

• Neovascular age-related macular degeneration
• vascular endothelial growth factor
• abicipar pegol
• choroidal neovascular membrane
• DARPin
• Designed Ankyrin Repeat Protein

Article highlights

• Despite impressive advancements in treatment of neovascular age-related macular degeneration over the past two decades with anti-VEGF therapy, there is a need to reduce the treatment burden associated with frequent intravitreal injections.

• DARPin molecules offer a number of potential advantages compared to antibodies or antibody fragments as potential therapeutics, including high affinity for their target, stability, and small molecular size.

• Abicipar pegol is a novel DARPin anti-VEGF agent that demonstrated the ability for greater than 90% of patients to maintain stable vision with 12-week dosing intervals in the phase III SEQUOIA and CEDAR trials, non-inferior to results obtained with monthly ranibizumab injection.

• Compared to ranibizumab, treatment with abicipar was associated with increased incidence of intraocular inflammation (IOI) in phase II and III trials. In the phase 3 program, through 1 year, 15.1–15.7% of patients treated with abicipar developed IOI compared with 0–0.6% of patients treated with ranibizumab. A modified manufacturing process was subsequently assessed in the 6-month MAPLE study, with a resulting IOI rate of 8.9%.

Declaration of interest

RM Hussain has served as an advisory board member for Alimera Sciences. CY Weng is a consultant for Allergan, Alcon, and Alimera Sciences. CC Wykoff is involved in research and consulting with Adverum, Allergan, Bayer, Chengdu Kanghong, Genentech/Roche, Kodiak, Novartis, and Regenxbio. SM Hariprasad is a consultant or on the speaker’s bureau for Allergan, Graybug, Novartis, OD-OS, Clearside Biomedical, EyePoint Pharmaceuticals, Alimera Sciences, Spark Therapeutics, and Regeneron. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.