Regeneron Pharmaceuticals, Inc. released positive results from a phase 3 clinical trial evaluating the use of EYLEA HD (aflibercept) injection 8 mg in patients diagnosed with macular edema following retinal vein occlusion (RVO) as well as central, branch, and hemiretinal vein occlusions.
The findings were presented during the virtual Angiogenesis, Exudation, and Degeneration 2025 annual meeting.
First: A rundown on EYLEA HD.
What it is: A vascular endothelial growth factor (VEGF) inhibitor administered as intravitreal (IVT) in joint development by Regeneron and Bayer AG (which owns exclusive marketing rights outside the U.S.).
- Regulatory status: EYLEA HD was granted FDA approval in August 2023 for the following retinal diseases:
- Wet age-related macular degeneration (AMD)
- Diabetic macular edema (DME)
- Diabetic retinopathy (DR)
To note: This marked Regeneron’s second FDA approval in the ophthalmic retina space, with the first being EYLEA 2 mg, indicated for retinopathy of prematurity (ROP) and those retinal diseases listed above.
Let’s talk dosing schedules.
EYLEA HD’s recommended dose is 8 mg (0.07 mL of 114.3 mg/mL solution) administered via IVT injection every 4 weeks (monthly) for the first 3 months followed by:
- For wet AMD and DME: 8 mg every 8 to 16 weeks (2 to 4 months)
- For DR: 8 mg every 8 to 12 weeks (2 to 3 months)
See here for its prescribing information (PI).
Next: How does this new phase 3 study differ from prior trials?
To start: The phase 3 QUASAR trial’s disease focus is on a new potential indication for which EYLEA HD is not (yet) approved—macular edema following RVO.
- For context: See here for details on the previous clinical findings for EYLEA HD, including extended dosing data for wet AMD and DME, as well as prolonged dosing for wet AMD alone.
Got it. Now tell me about the QUASAR study.
This phase 3 trial is a global double-masked, active-controlled trial seeking to evaluate the safety and efficacy of EYLEA HD versus EYLEA in patients with RVO.
The setup:
- Participants: 892 patients diagnosed with macular edema following RVO
- The design: Patients randomized into three groups to receive either:
- Group 1: EYLEA HD every 8 weeks following 3 initial monthly doses
- Group 2: EYLEA HD every 8 weeks following 5 initial monthly doses
- Note: The combined number of participants for these two groups was n = 591
- Group 3: EYLEA every 4 weeks (n =301)
- The study duration: 64 weeks
- The primary endpoint: Mean change in best-corrected visual acuity (BCVA) from randomization through Week 36, measured via Early Treatment Diabetic Retinopathy Study (ETDRS) letter score
Anything special to keep in mind with this setup?
There is indeed. Notably, patients randomized into the two EYLEA HD groups can potentially have their dosing intervals shortened to a minimum of every 4 weeks throughout the study’s duration if “protocol-defined criteria for disease progression are met.”
Additionally: These dosing intervals could also be extended based on protocol-defined criteria starting at:
- Week 32 for patients who receive EYLEA or EYLEA HD after 3 initial monthly doses
- Week 40 for patients who receive EYLEA HD after 5 initial monthly doses, with follow-up planned through Week 64
Noted. And these findings?
Overall: The study met its primary endpoint at 36 weeks—both EYLEA HD groups (dosed every 8 weeks) achieved non-inferior VA gains versus the EYLEA group (dosed every 2 weeks).
- Importantly: These EYLEA HD results were consistent across all studied diseases (including branch RVO and central retinal or hemiretinal vein occlusions).
For the EYLEA HD groups specifically: A total of 88% sustained an 8-week dosing regimen following the required 3 monthly doses, with 93% maintaining this regimen after completing 5 initial monthly doses.
How about EYLEA HD’s safety profile?
According to Regeneron: Both EYLEA HD and EYLEA groups “remained generally consistent” with the pre-established safety profile of EYLEA HD in its previous pivotal trials.
- As for adverse events (AEs): Treatment-emergent AEs occurred in ≥5% of all EYLEA HD patients, including increased ocular pressure (5%).
There was also:
- One case each of endophthalmitis and retinal vasculitis
- For EYLEA HD: 0.5% rate of intraocular inflammation (IOI)
- For EYLEA: 1.3% rate of IOI
And what’s the significance of this data?
Seenu M. Hariprasad, MD, chair of the Department of Ophthalmology and Visual Science at the University of Chicago and presenter of the findings, noted:
“Based on these new data, aflibercept 8 mg [EYLEA HD] may offer the potential to halve the number of injections needed, as compared to standard-of-care aflibercept 2 mg [EYLEA] and other anti-VEGF therapies.”
Sounds promising. So what’s next?
Regeneron reported plans to submit a supplementary Biologics License Application (sBLA) for EYLEA HD’s macular edema following RVO indication in Q1 2025.
To note: An sBLA is considered a follow-up to an original BLA for a new indication or treatment protocol that typically includes more extended data to support the updated claim.
- In this case: Since EYLEA HD’s original BLA was already approved for three retinal disease indications, this anticipated sBLA would add the RVO indication.
Nice! And in the meantime?
There’s more data! This time on EYLEA HD’s wet AMD (already approved) indication.
The 3-year results—from an extension study of the phase 3 PULSAR trial—were also presented during the Angiogenesis meeting. Check back this week for our coverage!