Aflibercept 8 mg Shows Durability at 3 Years in Wet AMD with W. Lloyd Clark, MD

Aflibercept 8 mg (EYLEA HD) achieved positive results at 3 years among patients with neovascular (wet) age-related macular degeneration (nAMD) in an extension study of the Phase 3 PULSAR trial.¹

Announced by Regeneron Pharmaceuticals on February 8, 2025, these findings, presented at Angiogenesis, Exudation, and Degeneration 2025, revealed most patients treated with aflibercept 8 mg continued to experience improvements in vision and anatomy, with extended dosing intervals.

“In the PULSAR extension, a large percentage of patients can be extended out to 4 months or even longer, with good disease control,” W. Lloyd Clark, MD, Palmetto Retinal Center, and assistant clinical professor of ophthalmology at the University of South Carolina School of Medicine told HCPLive. “This really does represent the next incremental improvement in the chronic treatment of patients with wet AMD.”

The US Food and Drug Administration (FDA) approved aflibercept 8 mg for wet age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy in August 2023.² Wet AMD occurs after the growth of abnormal blood vessels leak fluid under the macula, with nearly 1.4 million people in the US at risk of vision loss from AMD.³

The PULSAR trial was a double-masked, active-controlled pivotal trial in patients with wet AMD, reporting 88% of all patients on aflibercept 8 mg maintaining ≥3-month dosing intervals at the end of 2 years. After its completion, an optional extension study began at Week 96, with all participants receiving aflibercept 8 mg across Week 156. Dosing intervals in the extension study could be reduced or extended by 2-week increments based on certain criteria, with a minimum interval of every 2 months and a maximum of every 6 months.¹

Among those who completed the full 3 years of treatment (n = 375), nearly 60% had a last assigned dosing interval of ≥4 months. Approximately 40% and 24% had a final assigned dosing interval of ≥5 months and 6 months at the end of 3 years. Visual and anatomic improvements, including reductions in retinal thickness, were sustained through year 3 in the extension.

Those in the comparator arm were treated with aflibercept (EYLEA) as a fixed 2-month dosing regimen for 96 weeks and could switch to a 3-month dosing interval with aflibercept 8 mg until Week 156. Among those who completed the extension (n = 186) after switching, these data showed maintenance of vision and anatomic improvements, with 79% and 43% on an assigned dosing interval of ≥3 and ≥4 months, respectively.

The safety of aflibercept 8 mg was similar to aflibercept across 3 years and remained generally consistent with the known profile from pivotal trials. Ocular treatment-emergent adverse events (TEAEs) were reported in ≥4% of all patients, including cataracts, retinal hemorrhage, reduction of visual acuity, vitreous floaters, and increase of intraocular pressure. The rate of intraocular inflammation was 2.4% for the patients who switched from aflibercept to aflibercept, and 1.9% for those randomized at baseline.

“These patients typically stay on treatment for life and I’ve got patients in my clinic that have been on injections pushing 20 years,” Clark told HCPLive. “If we can reduce the number of treatment visits for these patients, it will significantly increase their quality of life. These patients with wet AMD are typically more compliant and so they welcome the idea of coming less frequently.”

Relevant disclosures for Clark include Amgen, Genentech/Roche, Regeneron, and others.

References

1. Three-year results for Eylea HD® (aflibercept) injection 8 mg in patients with wet age-related macular degeneration demonstrate continued durable vision gains and anatomic improvements with extended dosing intervals. Regeneron Pharmaceuticals Inc. February 8, 2025. Accessed February 20, 2025. https://newsroom.regeneron.com/news-releases/news-release-details/three-year-results-eylea-hdr-aflibercept-injection-8-mg-patients.

2. Campbell P. Aflibercept 8 mg (eylea HD) approved by FDA for wet AMD, DME, and Diabetic retinopathy. HCP Live. August 23, 2023. Accessed February 19, 2025. https://www.hcplive.com/view/aflibercept-8mg-eylea-hd-approved-by-fda-for-wamd-dme-and-diabetic-retinopathy.

3. Ruia S, Kaufman EJ. Macular Degeneration. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560778/