FDA Approves Regeneron's High-Dose Aflibercept, Eylea HD
In a major move that is expected to significantly extend dosing intervals for patients with retinal diseases, Regeneron received FDA approval for Eylea HD (aflibercept 8 mg) for patients with wet age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy (DR). The recommended dose for Eylea HD is 8 mg (0.07 mL of 114.3 mg/mL solution) every 4 weeks for the first 3 months across all indications, followed by 8 mg every 8 to 16 weeks in wet AMD and DME, and every 8 to 12 weeks for DR.
“The FDA approval of Eylea HD is an important advancement in retinal care,” Peter Kaiser, MD, Chaney Family Endowed Chair in Ophthalmology Research at the Cole Eye Institute and Professor of Ophthalmology at Cleveland Clinic Lerner College of Medicine, said in a company news release. “With Eylea HD, patients with wet age-related macular degeneration or diabetic retinal disease can now receive less frequent injections after their initial monthly doses and still experience the similar visual gains, anatomic improvements and safety profile of Eylea.”
Eylea HD will have a wholesale acquisition cost (WAC) of $2,625.00 per single-use vial. Regeneron stated that when used as indicated, the annualized list price of Eylea HD is anticipated to be "in the range of, or lower than, Eylea." Annual costs will vary based on several factors, including a patient’s prescribed dosing schedule. Regeneron stated it is committed to helping patients who have been prescribed Eylea HD access their medication.
The approval comes about a month after the FDA issued a complete response letter (CRL) to Regeneron declining to approve aflibercept 8 mg citing "an ongoing review of inspection findings at a third-party filler." In the CRL, the FDA did not identify any issues with the aflibercept 8 mg clinical efficacy or safety, trial design, labeling or drug substance manufacturing, and no additional clinical data or trials were requested. Regeneron said the CRL was issued solely due to unresolved observations resulting from an FDA inspection at a third-party contract manufacturing organization, Catalent, that the company engaged to complete vial-filling for aflibercept 8 mg.
Regeneron reported US sales of Eylea (aflibercept 2 mg) of $1.5 billion in the second quarter—about 7 percent lower than sales in the same quarter of 2022—but above estimates of $1.48 billion. Regeneron said the drop was primarily due to a lower net selling price driven by changing market dynamics, including increased competition.
The FDA approval of Eylea HD is based on the 48-week results of PULSAR and PHOTON – two double-masked, active-controlled pivotal trials evaluating Eylea HD compared to Eylea (aflibercept) injection 2 mg. Both the PULSAR trial in wet AMD (N=1,009) and PHOTON trial in DME (N=658) met their primary endpoint, with Eylea HD demonstrating noninferior and clinically equivalent vision gains at 48 weeks with both 12- and 16-week dosing regimens after 3 initial monthly doses, compared to an Eylea 8-week dosing regimen after initial monthly doses (3 in PULSAR and 5 in PHOTON). The vast majority of patients randomized at baseline to Eylea HD 12- or 16-week dosing regimens (following 3 initial monthly doses) were able to maintain these dosing intervals through 48 weeks.
The most common adverse reactions (≥3%) reported in patients treated with Eylea HD were cataract, conjunctival hemorrhage, intraocular pressure increased, ocular discomfort/eye pain/eye irritation, vision blurred, vitreous floaters, vitreous detachment, corneal epithelium defect, and retinal hemorrhage.
“More than 10 years ago, we fundamentally changed the way that certain serious retinal diseases were treated with the introduction of Eylea. With the approval of Eylea HD, we have elevated the high standard that Eylea set,” George D. Yancopoulos, MD, PhD, Board co-Chair, President and Chief Scientific Officer at Regeneron, and a principal inventor of Eylea, said in the news release. “Our continued commitment to retinal diseases resulted in an important scientific innovation – evolving the proven efficacy and safety of Eylea into a new treatment, Eylea HD, that provides lasting vision control with even fewer injections to further benefit those living with wet age-related macular degeneration or diabetic retinal diseases."
Eylea HD is being jointly developed by Regeneron and Bayer AG. In the U.S., Regeneron maintains exclusive rights to Eylea and Eylea HD. Bayer has licensed the exclusive marketing rights outside of the US, where the companies share equally the profits from sales of Eylea and Eylea HD following any regulatory approvals.
Regulatory filings for aflibercept 8 mg are under review in Europe and Japan. Submissions to other regulatory authorities in additional countries are also planned.