Biocon Biologics Limited and Samsung Bioepis / Biogen, Inc. have received FDA approval for their first-to-file application of YESAFILI (aflibercept-jbvf) and OPUVIZ (aflibercept-yszy), respectively—two interchangeable biosimilars for aflibercept injection 2 mg—commercially known as EYLEA (Regeneron, Inc).
Give me the rundown on Biocon, first.
As a subsidiary of Bangalore, India-based Biocon Ltd.—the country’s largest biopharmaceutical company founded in 1978—Biocon Biologics is developing, manufacturing, and commercializing cost effective biosimilars and generic formulations across the globe.
Its current portfolio includes 20+ biosimilars approved or in development, with eight currently commercialized, targeting +5.7 million patients in over 100 countries spanning North America, Europe, and Japan, Australia, and New Zealand (JANZ).
Talk more about this portfolio.
Biocon Biologics’ target therapeutic areas include:
- Bone health
- Diabetes
- Immunology
- Oncology
- Ophthalmology
The products: monoclonal antibodies and insulins
And how is it performing in the US market so far?
The company partnered with U.S.-based Mylan N.V. in 2009 to co-develop a biosimilar antibodies portfolio for global markets, which it has continued following Mylan’s 2019 merger with Upjohn, a Pfizer off-patent medicine division, to form Viatris Inc. in 2020.
More recently: In 2022, the company acquired Viatris’ global biosimilars business to become a fully integrated biosimilars company in the United States.
Gotcha. Now the other companies.
Launched in 2012, Samsung Bioepis is a biopharmaceutical company focused on developing and delivering a pipeline of biosimilar candidates in therapeutic areas such as ophthalmology, immunology, oncology, hematology, endocrinology, and gastroenterology.
Biogen, on the other hand, is a Massachusetts-based multinational biotechnology company focused on discovering, developing, and delivering neurological disease, autoimmune disorder, and cancer therapeutics
Now about this approval… talk about a “first-to-file application.”
This is essentially a generic abbreviated new drug application (ANDA) that’s exactly what it says it is: The first approval by the FDA of a specific drug that enables a manufacturer to market the product in the United States (before that brand name drug’s patents expires).
Note: This app must be submitted with a Paragraph IV certification, which acknowledges that a patent submitted to the FDA by the brand-name drug’s sponsor is (in the generic applicants’ opinion):
- Invalid
- Unenforceable
- Will not be infringed by the generic product
Plus: If approved, the first company (such as Biocon) to submit such an application is typically able to have exclusive rights to market the generic product for 180 days before other companies can introduce their own versions.
Now tell me about these drugs.
The generic equivalents of EYLEA—a vascular endothelial growth factor (VEGF) inhibitor approved by the FDA in 2011—are indicated for the ophthalmic treatment of patients with:
- Neovascular (wet) age-related macular degeneration (AMD)
- Macular edema following retinal vein occlusion (RVO)
- Branch or central RVO
- Diabetic macular edema (DME)
- Diabetic retinopathy (DR)
Note: Unlike EYLEA, YESAFILI and OPUVIZ are not indicated for retinopathy of prematurity (ROP), which the brand-name version was FDA approved for in February 2023.
What’re the recommended dosages?
For wet AMD: the 2 mg (0.05 mL of 40 mg/mL solution) therapeutic is intended to be intravitreally administered every 8 weeks following an initial monthly dose for 3 months.
For macular edema following RVO: 2 mg injected once every 4 weeks.
For DME and DR: 2 mg injected every 4 weeks for the first five injections, then 2 mg once every 8 weeks.
See here for EYLEA’s full prescribing information (PI).
Click here for YESAFILI’s PI and here for OPUVIZ’s PI.
Any warnings associated with these products?
Per the PIs for YESAFILI and OPUVIZ, intravitreal injections have been associated with:
- Endophthalmitis
- Retinal detachments
- Retinal vasculitis with/without occlusion
- Increase in intraocular pressure (IOP)
- Within 60 minutes of injection
- Arterial thromboembolic events (ATEs)
- Nonfatal stroke, nonfatal myocardial infarction, or vascular death
What about ocular adverse reactions?
Per EYLEA’s PI, participants in eight phase 3 clinical studies (for five different indications) reported the most common adverse events (AEs) occurring in greater than or equal to 5% of patients:
- Conjunctival hemorrhage
- Eye pain
- Cataract
- Vitreous hemorrhage
- Vitreous detachment
- Vitreous floaters
- Increase in IOP
See here (and scroll to 6.1 Clinical Trials Experience) for a breakdown of AEs by indication and studies.
So what’s significant about these approvals?
According to Biocon Biologic’s CEO and Managing Director Shreehas P. Tambe, YESAFILI marks the company’s entry into the ophthalmology space within the U.S.—building on its previous biosimilar approvals for:
- SEMGLEE (interchangeable insulin)
- OGIVRI (first biosimilar for Trastuzumab)
- FULPHILA (first biosimilar for Pegfilgrastim)
And broadly: These approvals for both YESAFILI and OPUVIZ are the first-ever interchangeables for EYLEA, offering patients potentially lower cost alternatives for seeking treatment.
Lastly … when will they be available?
No official word yet, so stay tuned for launch info later this year!