Sandoz Group AG announced that the FDA has approved Enzeevu (aflibercept-abzv) 2 mg as an interchangeable biosimilar for wet age-related macular degeneration (AMD).
Let’s start with Sandoz.
Established by Novartis in 2003, the Swiss-based company specializes in developing and commercializing generic pharmaceuticals and biosimilars for unmet medical needs.
- See its biosimilar portfolio.
Fast forward to 2022, Sandoz spun off from Novartis as a stand-alone, publicly traded company.
And by October 2023, it officially became an independent entity.
- Also of interest: Earlier this year, the company strengthened its ophthalmic biosimilar portfolio with the acquisition of Cimerli (ranibizumab-eqrn).
Now this biosimilar.
Packaged with a 2 mg vial kit and pre-filled syringe of aflibercept-abzv for intravitreal injection, Enzeevu is indicated to improve visual acuity (VA) in patients diagnosed with wet AMD.
Also: The FDA has provisionally (temporarily, in other words) determined that Enzeevu is interchangeable with its reference medicine due to it being “currently subject to an unexpired exclusivity for the first interchangeable biosimilar products,” Sandoz reported.
And its reference medicine is … ?
That would be Regeneron Inc.’s EYLEA (aflibercept injection), already FDA approved for the treatment of the following retinal diseases:
- Wet AMD
- Macular edema following retinal vein occlusion (RVO)
- Diabetic macular edema (DME)
- Diabetic retinopathy (DR)
- Retinopathy of prematurity (ROP)
I could’ve sworn we just heard about an EYLEA biosimilar approval …
Oh, you did. Last month, in fact, with the FDA’s approval of Formycon AG and Kling Biopharma GmbH’s FYB203/AHZANTIVE (aflibercept-mrbb).
- And before that, two more EYLEA biosimilars were approved in May 2024.
Alrighty then, let’s talk dosing.
As a biosimilar of EYLEA, Enzeevu’s recommended dosing schedule mirrors that of the reference drug’s wet AMD indication.
Per Enzeevu’s prescribing information (PI): The 2 mg (0.05 mL of 40 mg/mL solution) injection is intended to be intravitreally administered every 8 weeks following an initial monthly dose for 3 months.
- To compare: See here for EYLEA’s PI.
Any special notes on this?
Enzeevu’s PI emphasized that, while it may be dosed as frequently as every 4 weeks, “additional efficacy was not demonstrated in most patients when aflibercept was dosed every 4 weeks compared to every 8 weeks.”
In fact: Some patients may require dosing every 4 weeks (monthly) after the first 12 weeks (3 months)
- Further: While not as effective as the recommended 8-week dosing, “patients may also be treated with one dose every 12 weeks (3 months) after 1 year of effective therapy.”
How about precautions associated with use?
With ocular or periocular infection, active intraocular inflammation, and hypersensitivity noted as potential contraindications, the following precautions are also highlighted as potential complications that may occur following intravitreal injection:
- Endophthalmitis
- Retinal detachments
- Retinal vasculitis (with or without occlusion)
- Increase in intraocular pressure (IOP) within 60 minutes of injection
- Arterial thromboembolic events following intravitreal use of vascular endothelial growth factor (VEG) inhibitors
Now the clinical data this approval is based on.
Sandoz noted that the FDA’s approval is based on “the totality of evidence, including comprehensive analytical and preclinical in vitro study data” as well as the positive clinical findings from the phase 3 MYLIGHT study (NCT04864834).
Give me the rundown on that MYLIGHT study.
Here’s what to know about that confirmatory efficacy and safety trial.
- The design: multicenter, randomized double-masked, dual-arm, parallel trial
- The participants: 485 patients (aged 50+) with their study eye diagnosed with active choroidal neovascularization (CNV) lesions (type 1 and/or 2) secondary to AMD and/or retinal angiomatous proliferation lesions (type 3)
- The dosings: Enzeevu vs Eylea when intravitreally administered:
- First: Every 4 weeks (baseline, Weeks 4 and 8),
- Then: Every 8 weeks (Weeks 16, 24, 32, 40, 48)
- The outcome measures:
- Primary: Best-corrected visual acuity (BCVA) via Early Treatment of Diabetic Retinopathy Study (ETDRS) chart
- Secondary: See here
And the findings?
In August 2023, the company reported that the study met its primary efficacy endpoint and confirmed, “there is no clinically meaningful difference between the two products.”
Any adverse reactions linked to the therapeutic’s use?
Occurring in ≥5% of patients, the most common adverse reactions reported from eight phase 3 trials included:
- Conjunctival hemorrhage
- Ocular pain
- Cataract
- Vitreous detachment
- Vitreous floaters
- Transient rise in IOP (within 60 minutes of intravitreal injection)
Plus: See Enzeevu’s PI (Section 6.1, Table 1) for additional common adverse reactions (≥1%) based on two phase 2 trials comparing aflibercept to ranibizumab.
Lastly, when will Enzeevu be available in the U.S.?
No official word yet; however, Sandoz noted that a commercial launch will depend on several factors, including “the progress and outcome of pending or potential future related litigations or any potential settlements.”