Aflibercept: Applications for dosing duration and additional indications pending decision with FDA and EMA

(Image credit: AdobeStock/Anton)

Regeneron has proposed a longer dosing duration for the high-dose (HD) formulation of aflibercept (EYLEA HD). The FDA is expected to release is decision on this dosing duration by April 20, 2025.¹

This dosing extension information was shared during Regeneron’s presentation at the J.P. Morgan Healthcare Conference in January of 2025, noting that at the time of the presentation FDA was already reviewing its application for 24-week dosing for Eylea HD in wet age-related macular degeneration (AMD) and diabetic macular edema (DME). ²

The company has also filed an application with the FDA for the use of pre-filled syringes (PFS) of high-dose aflibercept with the US. Approval and launch of these PFS is expected by mid-2025.²

Aflibercept for RVO

It was also during this conference that the company noted that there are plans to submit a supplemental biologics license application (sBLA) for high-dose aflibercept with an up to 8-week dosing schedule for retinal vein occlusion (RVO). This comes after the completion of the phase 3 QUASAR trial of aflibercept 8 mg (EYLEA HD), which met its primary endpoint, in December of 2024.

QUASAR is a global, double-masked, active-controlled phase 3 trial evaluating the efficacy and safety of EYLEA HD, compared to EYLEA, in patients with RVO, including those with central, branch, and hemiretinal vein occlusions. In the trial, patients were treated with an 8-week dosing regimen of EYLEA HD, following 3 or 5 initial monthly doses, while EYLEA patients were treated every 4 weeks.³

Bayer announced the submission of an application to the European Medicines Agency (EMA) seeking to expand the indication for aflibercept 8mg. Aflibercept is being jointly developed by Bayer and Regeneron.⁴

Trial notes on high-dose aflibercept

The HD formulation is a longer-acting version of the original aflibercept drug and through less frequent injection, it is designed to be more convenient to the patient, reducing treatment burden. In August 2023, data from Regeneron’s Phase III PULSAR trial confirmed that even at dosing intervals at least 12 weeks long, high-dose Eylea did not sacrifice vision gains while also helping patients maintain their treatment schedules.¹

Positive 3-year results were shown from an extension study of the phase 3 PULSAR trial. According to the company, the longer-term wet age-related macular degeneration (wAMD) data demonstrated the vast majority of EYLEA HD patients who entered the extension study sustained the visual gains and anatomic improvements achieved by the end of the second year, while also achieving substantially longer treatment intervals. Additionally, patients who switched from EYLEA Injection 2 mg to EYLEA HD at the beginning of the third year were also able to maintain vision and anatomic improvements through the end of the third year, but with longer dosing intervals and fewer injections.⁵

Reference:

1. FDA Action Alert: Regeneron, Sanofi and Abeona. BioSpace. April 14, 2025. Accessed April 15, 2025. https://www.biospace.com/fda/fda-action-alert-regeneron-sanofi-and-abeona

2. Regeneron Provides Business Updates and Highlights from Broad Clinical Pipeline at the 43rd Annual J.P. Morgan Healthcare Conference. Regeneron. January 13, 2025. Accessed April 15, 2025. https://investor.regeneron.com/news-releases/news-release-details/regeneron-provides-business-updates-and-highlights-broad/

3. EYLEA HD® (aflibercept) Injection 8 mg Phase 3 Trial Meets Primary Endpoint Showing Improved Vision with Extended Dosing Intervals in Patients with Macular Edema following Retinal Vein Occlusion. Press Release; December 17, 2024. Accessed April 15, 2025. https://investor.regeneron.com/news-releases/news-release-details/eylea-hdr-aflibercept-injection-8-mg-phase-3-trial-meets-primary

4. Hayes, H. Bayer files EMA application for aflibercept 8mg in third indication, retinal vein occlusion. Modern Retina. April 9, 2025. Accessed April 14, 2025. https://www.modernretina.com/view/bayer-files-ema-application-for-aflibercept-8mg-in-third-indication-retinal-vein-occlusion

5. Harp, MD. Regeneron reveals positive results from multiple trials evaluating Eylea HD (aflibercept) injection 8 mg. Ophthalmology Times. February 10, 2025. Accessed April 15, 2025. https://www.modernretina.com/view/regeneron-reveals-positive-results-from-multiple-trials-evaluating-eylea-hd-aflibercept-injection-8-mg