Aflibercept 8 mg Noninferior for RVO in QUASAR with W. Lloyd Clark, MD

Positive results from the Phase 3 QUASAR trial demonstrate the noninferiority of aflibercept 8 mg (EYLEA HD) administered every 8 weeks to aflibercept 2 mg (EYLEA) dosed every 4 weeks for treating macular edema secondary to retinal vein occlusion (RVO).1

Announced by Regeneron Pharmaceuticals on February 8, 2025, these findings, presented at Angiogenesis, Exudation, and Degeneration 2025, will support the submission of a supplemental Biologics License Application (sBLA) in Q1 2025.

“A higher concentration of VEGF inhibition might be beneficial because we have seen situations where there’s an unmet need in people with active disease on monthly therapy,” W. Lloyd Clark, MD, Palmetto Retinal Center, and assistant clinical professor of ophthalmology at the University of South Carolina School of Medicine told HCPLive. “One of the key takeaways from QUASAR is that we do see an additional benefit, not only in terms of durability but also efficacy and the ability to get these eyes under control with less frequent injections.”

A common cause of vision loss in adults, RVO is the second most frequent retinal vascular disease, occurring when there is a blockage in a retinal vein, leading to restricted blood flow and increased pressure in the eye. Those with RVO can experience sudden blurry vision or loss of vision, with ultimate serious complications such as macular edema.2

The US Food and Drug Administration approved aflibercept 8 mg for wet age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy in August 2023.3 QUASAR is a global double-masked, active-controlled Phase 3 trial evaluating the efficacy and safety of aflibercept 8 mg in eyes with macular edema secondary to RVO, including central RVO (CRVO), branch RVO (BRVO), or hemiretinal RVO (HRVO).1

Patients were randomized into three groups to receive either aflibercept every 8 weeks after 3 initial monthly doses, aflibercept 8 mg every 8 weeks after 5 initial monthly doses, or aflibercept 2 mg every 4 weeks. The trial’s primary endpoint was the mean change in best-corrected visual acuity (BCVA) through week 36, as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score.

An analysis of QUASAR showed the trial met its primary endpoint, with both treatment cohorts of aflibercept 8 mg every 8 weeks achieving non-inferior BCVA gains to aflibercept 2 mg every 4 weeks. These results were consistent across patients with BRVO, CRVO, and HRVO. At 36 weeks, 88% of patients sustained an 8-week aflibercept 8 mg dosing schedule after 3 loading doses, increasing to 93% after 5 loading doses.

Aflibercept 8 mg’s safety remained consistent with the known profile from pivotal trials, including low rates of intraocular inflammation (0.5%). Ocular treatment-emergent adverse events (TEAEs) were reported in ≥5% of all aflibercept 8 mg-treated patients, including increased ocular pressure (5%) and a single case each of endophthalmitis and retinal vasculitis.

“We’ve got ~15 years of clinical experience with the aflibercept molecule for the 2 mg formulation. Now, we’ve got a good body of evidence of 8 mg experience as well, and it appears that the safety profile of the 8 mg formulation is very similar to the 2 mg,” Clark told HCPLive. “Our confidence in the safety of the molecule appears to be pretty much irrespective of the concentration.”

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

References

1. Eylea HD® (aflibercept) injection 8 mg positive phase 3 results in patients with macular edema following retinal vein occlusion presented at Angiogenesis meeting. Regeneron Pharmaceuticals Inc. February 8, 2025. Accessed February 19, 2025. https://newsroom.regeneron.com/news-releases/news-release-details/eylea-hdr-aflibercept-injection-8-mg-positive-phase-3-results.
2. Blair K, Czyz CN. Central Retinal Vein Occlusion. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525985/
3. 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.