Regeneron Pharmaceuticals, Inc. announced positive 3-year data on EYLEA HD (aflibercept) injection 8 mg for wet age-related macular degeneration (AMD) from an extension study of the phase 3 PULSAR trial.
These findings were presented during the virtual Angiogenesis, Exudation, and Degeneration 2025 annual meeting—coinciding with the company’s recent reporting of positive phase 3 data supporting the proposed indication of EYLEA HD for macular edema following retinal vein occlusion (RVO).
Given the recent coverage on EYLEA HD, give me a very brief rundown.
FDA-approved in 2023, EYLEA HD is currently indicated for the following retinal diseases:
- Wet AMD (our topic of discussion)
- Diabetic macular edema (DME)
- Diabetic retinopathy (DR)
Notably: EYLEA HD’s regulatory clearance was preceded by EYLEA (aflibercept) 2 mg, Regeneron’s first ophthalmic retinal approval, indicated for wet AMD, DME, DR, and retinopathy of prematurity (ROP).
See here for details on how EYLEA HD and EYLEA’s dosing schedules differ.
Let’s talk about this phase 3 trial.
The randomized, double-masked, active-controlled PULSAR (NCT04423718) study was one of two phase 3 trials (the other being the PHOTON study [NCT04429503] for DME) with positive data that supported the approval of EYLEA HD.
- Specifically: The PULSAR study evaluated aflibercept 8 mg (EYLEA HD) for its wet AMD indication against aflibercept 2 mg (EYLEA).
The setup:
- Participants: (n = 1,009)
- The design: Patients were randomized into three groups to receive either EYLEA HD at 12- and 16-week intervals, or EYLEA every 8 weeks
- To note: For EYLEA HD patients: If pre-specified criteria were met, dosing intervals could be shortened throughout the trial or extended in the second and third years of the study
And the initial findings?
One-year data found the study met its primary endpoint:
- Non-inferiority in vision gains for EYLEA HD-treated patients during 12- and 16-week dosing regimens following initial monthly dosing regimens at 48 weeks compared to 8 weeks of dosing in patients treated with an EYLEA injection.
- These patients achieved clinically equivalent vision gains versus EYLEA.
Two-year data (as we reported in August 2023) found:
- The majority of EYLEA HD-treated patients were able to maintain or further extend their dosing interval (see here for the numbers, including 88% of patients on a ≥12-week dosing interval at the end of 2 years).
Interesting … and how does this new 3-year data compare?
To start: Regeneron reported that the “vast majority of patients maintained visual and anatomic improvements” while also achieving substantially longer treatment intervals—including dosing regimens of twice a year.
- The numbers: The following percentages of EYELA HD-treated patients (n =375) achieved last assigned dosing intervals at the following months:
- 77% of ≥3 months
- 58% of ≥4 months
- 40% of ≥5 months
- 24% of 6 months
What do we know about the EYLEA-treated patients who switched to EYLEA HD?
These patients initially received EYLEA as a fixed 2-month dosing regimen following three initial monthly doses for a total of 96 weeks.
- After this: Participants were given the option to enter the extension study at Week 96 and were then switched to a 3-month dosing interval of EYLEA HD.
And what were their visual outcomes?
Those patients who switched at the beginning of Year 3 were “also able to maintain vision and anatomic improvements” that extended to the end of that year.
- Most notably: They achieved this ”with longer dosing intervals and fewer injections.”
The numbers:
- 186 of EYLEA-switched patients completed the extension
- 79% and 43% of these patients had a last assigned dosing interval of ≥3 and ≥4 months, respectively, at Week 156
Got it. Now let’s talk safety profile of EYLEA HD.
Regeneron reported the drug’s safety profile to be “similar to EYLEA” through the extension’s 3-year period, remaining “generally consistent with the known safety profile” it had demonstrated in previous clinical trials.
The specifics:
- Ocular treatment-emergent adverse events (AEs) developed in ≥4% of all patients, including:
- Cataract
- Retinal hemorrhage
- Visual acuity reduction
- Vitreous floaters
- Intraocular pressure (IOP) increase
- 2.4% rate of intraocular inflammation (IOI) among patients who switched from EYLEA to EYLEA HD
- 1.9% rate of IOI for EYLEA HD randomized at baseline
Sounds promising … and how does this compare to its 3-year data for DME?
Similar and just as promising.
In fact, the company stated the results add to a growing body of evidence demonstrating EYLEA HD’s ability to extend dosing intervals. Case in point: Its DME findings found that:
88%, 68%, 48%, and 28% of patients achieved a last assigned dosing interval of ≥3, ≥4, ≥5, and 6 months, respectively.