Regeneron Pharmaceuticals, Inc. announced that The Lancet has published 1-year data from the pivotal PULSAR and PHOTON trials assessing the use of EYLEA HD (aflibercept 8 mg) in patients diagnosed with neovascular (wet) age-related macular degeneration (AMD) and diabetic macular edema (DME).
First, talk about aflibercept 8 mg.
Jointly developed by Regeneron and Bayer AG (with exclusive U.S. rights belonging to Regeneron), EYLEA HD (not to be confused with Eylea, aflibercept 2 mg) is a vascular endothelial growth factor (VEGF) inhibitor administered as an intravitreal injection .
The formulation was most recently FDA approved in August 2023 as Regeneron’s second FDA-approved ophthalmic medication in the retina space (with the first being EYLEA) for the following retinal diseases:
- Wet AMD
- DME
- Diabetic retinopathy (DR)
See here for full prescribing information.
How does this compare to EYLEA?
Aside from containing a higher dose of aflibercept (8 mg vs 2 mg), EYLEA is also approved for two more indications:
- Macular edema following retinal vein occlusion (RVO)
- Retinopathy of prematurity (ROP) in preterm infants
- FDA approved in February 2023 (prescribing info here)
How do the dosing schedules compare?
The recommended dose for EYLEA HD is 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 and DME
- 8 mg every 8 to 16 weeks (2 to 4 months)
- DR
- 8 mg every 8 to 12 weeks (2 to 3 months)
Comparison: EYLEA 2 mg follows the same dosing schedule; however, the ROP dosing is recommended as 0.4 mg via intravitreal injection 6-8 times a year.
Noted. So tell me about these trials.
The global multicenter, double-masked, active-controlled, pivotal phase 3 clinical trials included:
- PULSAR (NCT04423718) for wet AMD
- n = 1,009
- PHOTON (NCT04429503) for DME
- n = 658
Participants were randomized into three groups to receive either EYLEA HD at 12- and 16-week intervals, or EYLEA every 8 weeks.
How did EYLEA perform?
Each trial met its primary endpoints, reporting positive 2-year (48-week) data in measuring the safety and efficacy of EYLEA (aflibercept) 2 mg compared to EYLEA HD 8 mg.
See here and here for details on the PUSLAR and PHOTON trials data, respectively.
Gotcha. So what did this 1-year EYLEA HD data show?
Per Regeneron, 48-week results indicated that both studies also met their primary endpoints for Eylea HD, with extended 12- or 16-week dosing regimens demonstrating “non-inferior vision gains to standard of care EYLEA (after three initial monthly doses) … with fixed 8-week dosing in patients with wet AMD and DME in the first year.”
Give me some numbers.
For both trials, the following percentages of participants were noted as maintaining extended dosing intervals through 48 weeks after being randomized to the following dosings:
- 79% and 77% of wet AMD patients at 12-week dosing
- 91% and 89% of patients at 16-week dosing
Any adverse events?
The most common adverse events occurred in less than 3% of participants, the company reported. These included:
- Cataract
- Conjunctival hemorrhage
- Intraocular pressure (IOP) increase
- Ocular discomfort
- Eye pain
- Eye irritation
- Blurry vision
- Vitreous floaters
- Vitreous detachment
- Corneal epithelium defect
- Retinal hemorrhage
And overall?
According to the company: “EYLEA HD has shown impressive durable visual improvements and rapid and resilient fluid control with a safety profile comparable to EYLEA.”
Significance?
With extended dosing intervals of 12 and 16 weeks and fewer injections needed vs other wet AMD / diabetic retinal disease therapeutics, EYLEA HD has the potential to “substantially reduce treatment burden for patients,” Regeneron noted.