New 96-week research presented at the 2024 Association for Research in Vision (ARVO) annual meeting earlier this month investigated the use of aflibercept 8 mg vs aflibercept 2 mg for treating patients with treatment-naïve neovascular (wet) age-related macular degeneration (nAMD; wet AMD).
Let’s start with these dosages.
Developed by Regeneron and Bayer AG (with exclusive U.S. rights belonging to Regeneron), EYLEA HD (aflibercept 8 mg) is a vascular endothelial growth factor (VEGF) inhibitor administered as an intravitreal injection .
The formulation was FDA approved in August 2023 as Regeneron’s second FDA-approved ophthalmic medication in the retina space or the following diseases:
- Wet AMD
- Diabetic macular edema (DME)
- Diabetic retinopathy (DR)
See here for full prescribing information.
Now aflibercept 2 mg.
Developed prior to EYLEA HD, EYLEA (aflibercept 2 mg) is already FDA approved for two additional indications:
- Wet AMD
- DME
- Macular edema following retinal vein occlusion (RVO)
- Retinopathy of prematurity (ROP)
- DR
And their respective dosing schedules?
EYLEA HD: 8 mg (0.07 mL of 114.3 mg/mL solution) administered via intravitreal injection every 4 weeks (monthly) for the first 3 months followed by:
- Wet AMD / DME: 8 mg every 8 to 16 weeks (2 to 4 months)
- DR: 8 mg every 8 to 12 weeks (2 to 3 months)
EYLEA: administered every 8 weeks following an initially monthly dose for 3 months schedule; however, the ROP dosing is recommended as 0.4 mg via intravitreal injection 6-8 times a year.
Gotcha. What else should I know about?
The global, multicenter, double-masked, active-controlled, randomized pivotal phase 3 PULSAR trial (NCT04423718), which evaluated 1,011 wet AMD patients.
The setup: Participants were randomly assigned (1:1:1) to receive either EYLEA HD or EYLEA
The study duration: 12- and 16-week dosing intervals (EYLEA HD) or 8-week dosing intervals (EYLEA) following three initial monthly injections
And the number of participants?
- EYLEA HD
- 12 weeks (n = 335)
- 16 weeks (n = 338)
- EYLEA
- 8 weeks (n = 336)
So what did the original wet AMD data find?
There’s two sets of data to know about from the PULSAR trial: The first: Reported in August 2023, positive 2-year topline data found the majority of wet AMD patients randomized to be treated with EYLEA HD were able to maintain or further extend their dosing interval. See here for stats.
The second: Reported in March 2024, 1-year extended dosing data found that 79% and 91% of wet AMD patients receiving EYLEA HD maintained extended dosing intervals at 12 and 16 weeks, respectively. More details here.
Now to this new research.
Important to know: From Week 52 to Week 96, dosing schedules for the EYLEA HD participants could be extended (as needed) based on study criteria.
Give me these 96-week stats.
A total of 75% and 70% EYLEA HD participants maintained their 12- and 16-week dosing intervals, respectively.
Per the presenters: In the combined (EYLEA HD) arm, 47% of patients who completed 96 weeks had dosing intervals of ≥20 weeks at Week 96; 28% had a 24-week dosing interval at Week 96.
Plus: No new safety signals were identified with this dosage.
How about for BCVA?
From baseline at Week 96, the least squares mean (SE) change in best-corrected visual acuity (BCVA) was reported at +6.6 (0.73), +5.6 (0.77), and +5.5 (0.75) Early Treatment Diabetic Retinopathy Study (ETDRS) letters for EYLEA (8 weeks), EYLEA HD (12 weeks), and EYLEA HD (16 weeks), respectively.
And overall?
The presenter concluded that EYLEA HD at 12-week dosing intervals maintained similar BCVA gains—with a similar safety profile—vs EYLEA at 8-week dosing in wet AMD patients.
Even further: “Almost half of all patients in the combined (EYLEA HD) arm who completed 96 weeks of treatment qualified for extended dosing intervals of ≥20 weeks.”
Conclusions?
The study authors noted that this latest data suggest EYLEA HD may reduce the need for frequent injections in wet AMD patients.