FDA Approves New Aflibercept Indication Ahead of Competition

The FDA this week approved Regeneron’s aflibercept (Eylea) to treat all stages of diabetic retinopathy. The regulatory decision makes aflibercept the only anti—vascular endothelial growth factor (anti-VEGF) therapy approved for 2 dosing regimens in this indication: every 8 weeks or every 4 weeks.

Approval of the anti-VEGF therapy in this new indication was based on results of the PANORAMA trial.

PANORAMA, a phase 3 clinical trial in 402 patients with nonproliferative diabetic retinopathy without diabetic macular edema, had 3 arms: an observational sham injection group and 2 treatment groups, dosed every 8 weeks or every 16 weeks, respectively. The primary end point was the proportion of patients who experienced a 2-step or greater improvement in the diabetic retinopathy severity scale (DRSS) from baseline by week 52.

In the 16-week treatment group, 65% of patients had 2 or more steps of improvement from baseline, and 80% of the 8-week treatment group had 2 or more steps of improvement. In the sham injection group, 15% of patients had similar improvement.

The newly approved indication comes as aflibercept faces oncoming challenges from both novel agents and biosimilar challengers. In April 2019, the FDA granted priority review to Novartis’ innovator biologic, RTH258, brolucizumab. This novel biologic is intended to treat wet age-related macular degeneration, an indication that aflibercept also holds. Brolucizumab, which is a humanized single-chain antibody fragment with enhanced tissue penetration and rapid clearance from systemic circulation, has been shown to be more effective in reducing disease activity and retinal fluid than aflibercept.

At the same time as Regeneron hopes to defend its market share from brolucizumab, should it be approved, biosimilars of the blockbuster aflibercept also threaten the $1.68 billion in annual sales that the company generates from the brand-name Eylea.

Republic of Korea—based Alteogen recently secured a process patent for its aflibercept biosimilar, which it says has better resilience to high temperatures and a longer shelf life than the innovator drug. Additionally, Momenta and Mylan entered a phase 3 pivotal trial of a biosimilar aflibercept candidate in late 2018.

Coherus BioSciences is also advancing an aflibercept candidate as well as a ranibizumab candidate, referencing another anti-VEGF agent, Lucentis. Xbrane Biopharma and Samsung Bioepis are also both working on biosimilars of ranibizumab. Finally, bevacizumab, used off-label, is also widely used in treating eye disorders, and has 1 FDA-approved (although not yet launched) biosimilar.