What to Know About the EYLEA Biosimilars

What to Know About the FDA-Approved EYLEA (aflibercept) Biosimilars

The Food and Drug Administration(FDA) approved two interchangeable EYLEA biosimilars on Monday, May 20th. This encourages the potential for greater patient accessibility to drugs for the treatment of wet age-related macular degeneration, macular edema, diabetic retinopathy, and other ophthalmic conditions. However, with the approval of these biosimilars comes new challenges for providers.

These can include staying current with medication coding, pricing information, and knowledge of the new biosimilar treatments so you can administer high-quality care, efficiently conduct benefits investigations, and submit insurance claims. Today, we’ll discuss EYLEA and the new biosimilars YESAFILI and OPUVIZ, including how they impact your practice and the pricing of EYLEA for the treatment of ophthalmic conditions.

EYLEA Indications, Mechanism of Action, and Administration

EYLEA, the brand name of the drug aflibercept, is indicated for use in patients with neovascular(wet) age-related macular degeneration(nAMD), diabetic retinopathy (DR), and diabetic macular edema (DME).

Like AVASTIN (bevacizumab), which is used to treat certain ophthalmic diseases off-label, EYLEA can treat off-label ophthalmic diseases, including macular edema following retinal vein occlusion(RVO) and choroidal neovascularization. It can also slow vision loss in certain patient populations.

Aflibercept acts as a decoy receptor for placental growth factor(P1GF) and vascular endothelial growth factor-A(VEGF). P1GF acts via VEGFR-1, and VEGF acts via VEGFR-1 and VEGFR-2. Activation of these two receptors can lead to increased vascular permeability and neovascularization. When Aflibercept binds both P1GF and VEGF, it prevents the binding and subsequent activation of the cognate VEGF receptors.

Aflibercept is only indicated for ophthalmic intravitreal injection, with two recommended doses. It was FDA-approved in 2011 at a dosage of 2mg (0.05 mL of 40mg/mL solution) monthly for the first three months of treatment. After the first three months, it is recommended at the same dosage(2mg) once every two months for the duration of treatment.

EYLEA HD was FDA-approved in 2023 at a dosage of 8 mg (0.07 mL of 114.3 mg/mL solution) monthly for 3 months, followed by 8 mg(0.07 mL of 114.3 mg/mL solution) injections every 8-16 weeks indicated for nAMD and DME and every 8-12 weeks for DME.

FDA-Approved Biosimilars YESAFILI and OPUVIZ

YESAFILI (Aflibercept-JBVF) and OPUVIZ (Aflibercept-YSZY) are produced by Biocon Biologics and Samsung Bioepis, respectively. Both were approved with interchangeability designations, but it’s uncertain when they’ll launch in the US.


YESAFILI Medication Details

YESAFILI is indicated and FDA-approved for treating nAMD, macular edema following RVO, DME, and DR. As a biosimilar medication to EYLEA, YESAFILI exhibits the same mechanism of action.

While it is safe and effective for pediatric patient populations in indications for which EYLEA is approved, it is not approved for use in pediatric populations due to EYLEA’s marketing exclusivity.

YESAFILI administration and dosage recommendations are the same as those for EYLEA: intravitreal 2 mg(0.05 mL of 40mg/mL solution) monthly for the first three months and 2 mg every two months thereafter. Unlike EYLEA, YESAFILI is not approved at a higher dosage.

There are expanded administration recommendations for the additional disorder YESAFILI is indicated and approved to cover (RVO) and additional recommendations for AMD.

  • AMD: While the standard recommendation is to move to injections once every 8 weeks after three months of injections once every four weeks, it may be necessary to administer YESAFILI every 4 weeks after the first 12 weeks of treatment. Additionally, patients can be treated with one dose every 12 weeks after a year of effective therapy, although this is not as effective as treatment every 8 weeks.
  • RVO: 2 mg (0.05 mL of 40 mg/mL solution) administered intravitreal injection once every 4 weeks or approximately every 25 days.

OPUVIZ Medication Details

OPUVIZ is also indicated and FDA-approved for the treatment of nAMD, macular edema following RVO, DME, and DR. As EYLEA’s biosimilar, it has the same mechanism of action, VEGF inhibition.

It has the same dosing and administration recommendations that YESAFILI expands on regarding nAMD and RVO and the same dosing and administration recommendations as EYLEA for DR and DME. Like YESAFILI, it is not approved at a higher dosage than 2 mg(0.05 mL of 40 mg/mL solution).


EYLEA Patent Expiration and Biosimilar Product Development

Regeneron’s regulatory exclusivity period for EYLEA ended on May 17th, 2024. However, they still hold several patents, some of which may not expire until 2032. At this point, they have three formulation patents in the U.S. due to expire between March 2026 and June 2027 and one formulation patent in Europe that will expire in June 2027.

There are also three methods of treatment patents for EYLEA that will expire between January and May 2032 and a manufacturing patent that ends in March 2026.

With the patents EYLEA still holds, Regeneron has taken Samsung Biologics to court in a patent litigation case and settled with Biocon Biologics so YESAFILI could go to market in Canada in 2025. For both YESAFILI and OPUVIZ, there’s no indication of when they’ll come to market in the U.S. yet.

How The FDA-Approved Biosimilars Will Impact Providers and Drug Pricing

The approval of YESAFILI and OPUVIZ currently has no impact on U.S. healthcare providers because they aren’t on the market in the U.S. However, when they go to market, providers will gain additional treatment options for patients with any of the diseases these medications are indicated for. They’ll also need to familiarize themselves with billing codes (biosimilar codes all start with Q5) and reimbursement policies.

When discussing YESAFILI and OPUVIZ’s impact on providers, it’s important to address the complexity of biosimilar pricing. While biosimilars are an important route to driving down biologics’ cost, calculating biosimilars’ reimbursement rates can be complex.

Providers will need to become familiar with calculating reimbursement rates accurately if prescribing YESAFILI and OPUVIZ. That’s why BuyandBill.com provides coding and pricing information in an easily accessible, cost-effective format—to ensure costs can be easily analyzed and claims submitted accurately.

Stay Updated on Drug Codes & Pricing with BuyandBill.com

The FDA approved two EYLEA biosimilars three days after Regeneron’s market exclusivity ended. This currently has no impact on providers, with the date of these two EYLEA biosimilars coming to market in the U.S. up in the air. However, healthcare providers who treat macular degeneration and other eye conditions must be familiar with these biosimilars sooner rather than later.

BuyandBill.com aims to make claims completion and submission as quick and accurate as possible so your patients can get the care they need, and you can get reimbursed. Our pricing and coding information database makes it easy for you to focus on doing what you do best by streamlining the efficiency of your billing process. Sign up for a subscription today.