Celltrion, Inc. has received FDA approval for EYDENZELT (aflibercept-bova)—a biosimilar referencing Regeneron Pharmaceuticals’ EYLEA (aflibercept).
To note: This approval is Celltrion’s first in ophthalmology.
Let’s start with Celltrion.
With U.S. headquarters in New Jersey, the South Korean biopharmaceutical company's primary focus lies in developing and delivering affordable, advanced biologics for patients.
- See here to learn more about the global company and its U.S. arm.
Before we get to this biosimilar, let’s talk about its name-brand counterpart.
First approved by the FDA in 2011 (and most recently in 2023), EYLEA is a vascular endothelial growth factor (VEGF) inhibitor indicated to treat the following retinal diseases:
- Wet age-related macular degeneration (AMD)
- Macular edema following retinal vein occlusion (RVO)
- Diabetic macular edema (DME)
- Diabetic retinopathy (DR)
- Retinopathy of prematurity (ROP)
Check out its prescribing information (PI) for details on recommended dosages (Administered via intravitreal [IVT] injection) for each indication.
Now to EYDENZELT.
As an EYLEA biosimilar (see here for what that means), EYDENZELT is an IVT-administered VEGF inhibitor with the exact same indications and dosages as EYLEA—save for one exception:
- The therapeutic isn’t indicated for ROP.
Are its recommended dosages the same, though?
Indeed. According to its PI, the following dosages are recommended:
- Wet AMD: 2 mg (0.05 mL of 40 mg/mL solution) every 4 weeks for the first 3 months, then 2 mg once every 8 weeks
- Macular edema following RVO: 2 mg (0.05 mL of 40 mg/mL solution) every 4 weeks
- DME and DR: 2 mg every 4 weeks for the first five injections, then 2 mg (0.05 mL of 40 mg/mL solution) once every 8 weeks
Noted. Any contraindications to be aware of?
A few—patients with ocular or periocular infections, active intraocular inflammation, and hypersensitivity.
- Regarding that last condition: A hypersensitivity reaction could potentially develop as a rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation (IOI).
How about warnings or precautions?
Per its PI, IVT-administered injections (particularly in aflibercept products) were noted as having an association with:
- Endophthalmitis
- Retinal detachments
- Retinal vasculitis (with or without occlusion, though rare)
- Intraocular pressure (IOP) increase within 60 minutes of injection
- Arterial thromboembolic events
And while we’re at it, any potential adverse events?
Outside of those already discussed? None were called out.
However, EYDENZELT’s PI noted that phase 3 clinical trials conducted on 2 mg aflibercept among nearly 2.4K reported the following most common adverse reactions (occurring in ≥5% of aflibercept-administered patients):
- Conjunctival hemorrhage, eye pain, cataract, vitreous detachment and floaters, and increased IOP
Speaking of clinical trials … what clinical evidence was this approval based on?
According to Celltrion: “A totality of evidence including analytical, nonclinical, and clinical data.”
The company referenced a 52-week phase 3 study (NCT04739306) evaluating EYDENZELT’s safety, pharmacokinetics, and immunogenicity as secondary endpoints compared to EYLEA among 348 DME patients.
- The primary endpoint: Change in best-corrected visual acuity (BCVA) measured at week 8 from baseline, comparing EYDENZELT and EYLEA.
And those results?
EYDENZELT met the study’s “predefined equivalence criteria” for EYLEA.
As for secondary endpoints: These reportedly also showed “similar trends” to those of the name-brand therapeutic.
Nice! Now, I have to ask—didn’t Regeneron file a lawsuit to prevent this approval?
Good memory … and yes, actually. In fact, Regeneron has been involved in several legal moves (largely patent infringement cases) to prevent other EYLEA biosimilars from entering the U.S. marketplace.
Interesting … and when will EYDENZELT be available?
No word on that yet, so stay tuned!