Regeneron Pharmaceuticals, Inc., in collaboration with Bayer AG, has received FDA approval for Eylea HD (aflibercept) Injection 8 mg for the treatment of patients with wet age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy (DR).
Refresh me on aflibercept first.
Aflibercept is in a medication class of vascular endothelial growth factor A (VEGF-A) and placental growth factor (PIGF) antagonists that stops the growth of abnormal blood vessels and leakage in the eyes in patients diagnosed with retinal diseases.
And aflibercept 8 mg?
Administered via intravitreal injection, the high-dose drug has been developed as a joint partnership between Regeneron and Bayer AG. Regeneron owns exclusive rights to both Eylea (aflibercept 2 mg) and aflibercept 8 mg in the United States, while Bayer has licensed the exclusive marketing rights outside of the country.
To note, both companies are currently equally splitting sales profits from Eylea and will follow suit for any future sales of aflibercept 8 mg (pending regulatory approval).
I thought the FDA rejected this high-dose version?
Not the drug—just its Biological License Application (BLA).
Back in June 2023, the FDA rejected the BLA for Eylea HD via a complete response letter (CRL), citing an ongoing review of inspection at a third-party manufacturer.
To note, the agency reported no issues with the drug’s “clinical efficacy or safety, trial design, labeling or drug substance manufacturing.”
Then what?
Regeneron announced on August 18, 2023, that its pre-approval inspection issues raised in the CRL relating to Eylea HD had been addressed.
Further, the FDA is expected to make a determination on the BLA within the next few weeks.
Remind me .. isn’t Eylea already approved?
Yes, but for a lower dosage: 2 mg. That concentration level is indicated for:
- Wet AMD
- DME
- Macular edema following retinal vein occlusion (RVO)
- DR
Eylea (aflibercept) 2 mg was also recently approved in February 2023 for the treatment of retinopathy of prematurity (ROP) in infants.
See here for the full prescribing info.
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)
For comparison, Eylea 2 mg follows the same dosing schedule; however, the dosing for ROP is recommended as 0.4 mg via intravitreal injection 6-8 times a year.
Gotcha. Any clinical data on it?
The approval is based on two global multicenter, double-masked, active-controlled, pivotal phase 3 clinical trials: PULSAR (NCT04423718) for wet AMD and PHOTON (NCT04429503) for DME.
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. See here and here for details on the PUSLAR and PHOTON trials data, respectively.
Any adverse effects?
Between both trials, the most common adverse reactions—occurring in ≥3%—treated with Eylea HD included:
- Cataract
- Conjunctival hemorrhage
- Intraocular pressure (IOP) increase
- Ocular discomfort/eye pain/eye irritation
- Blurred vision
- Vitreous floaters
- Vitreous detachment
- Corneal epithelium defect
- Retinal hemorrhage
Significance?
With fewer injections needed compared to other wet AMD and diabetic retinal disease treatments, Eylea HD is now the company’s second FDA-approved ophthalmic medication in the retina space (with the first being Eylea).
So how much does it cost?
Per Regeneron, Eylea HD is priced at $2,625 per single-use vial in the United States.
When used as indicated, the annualized list price of Eylea HD is expected to be "in the range of, or lower than, Eylea."
And when will it be available?
The company hasn’t yet given a time frame… stay tuned!