FDA approves biosimilars Yesafili and Opuviz for Diabetic Macular Edema, offering affordable treatment options.
Breakthrough in Diabetic Macular Edema Treatment
May 25th, 2024: The FDA’s recent approval of two new biosimilars, Yesafili (aflibercept-jbvf) and Opuviz (aflibercept-yszy), marks a significant breakthrough in the treatment of Diabetic Retinopathy. These biosimilars are interchangeable with Eylea (Aflibercept), a biologic drug used to treat wet age-related macular degeneration (AMD) and Diabetic macular edema (DME).
What is Diabetic Macular Edema?
Diabetic macular edema is a debilitating eye condition that affects millions worldwide, causing vision impairment and blindness. According to a 2018 study, it affects 4.2% to 7.9% of individuals with type-1 diabetes and 1.4% to 12.8% of those with type-2 diabetes (Lee, 2015). In the United States alone, almost 19.8 million Americans have age-related macular degeneration (AMD) (Rein, 2019).
Macular edema occurs when thin, damaged, or leaky blood vessels in the central part of the retina (macula) lead to fluid accumulation, swollen macula, and blurry vision. If left untreated, it can result in vision loss (Tranos, 2004).
Evolution of Treatment Options
Over the last two decades, the treatment of Diabetic macular edema has shifted from multisession Focal-Grid Macular Laser Surgery to chemical treatment. Researchers have focused on developing drugs that target Vascular Endothelial Growth Factor (VEGF) to stabilize blood vessels in the macula and prevent new ones from growing (Virgili, 2018). From February 2004 till October 2023 FDA approved six biologic anti-VEGF drugs for DME treatment; Avastin (2004), Lucentis (2006) Iluvien (2014), Ozurdex (2009), Eylea (Aug 2023) and Vabysmo (Oct 2023).
New Interchangeable Biosimilars: Yesafili and Opuviz
This year on 20th May, FDA approved two new interchangeable biosimilars to Eylea, Yesafili and Opuviz. A biosimilar is a biological product that is highly similar to an already approved reference product, with no clinically meaningful differences in safety and effectiveness. An interchangeable biosimilar meets additional requirement, allowing pharmacy-level substitution without consulting the prescriber. Yesafili (Biocon) and Opuviz (Samsung Bioepis) are administered by intravitreal injection monthly, with a recommended dose of 2 mg (0.05 mL) for the first 5 months and then bimonthly for the next 4-5 months.
Image: Biocon and Samsung Biopesis developed the two new Biosimilars
Clinical Studies, Efficacy and and Adverse Reactions
In a comprehensive analysis of eight phase 3 studies, a total of 2980 adult patients were treated with aflibercept, with 2379 receiving the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure were rare, occurring in less than 0.1% of intravitreal injections with both the biosimilars. These reactions included endophthalmitis and retinal detachment, which are serious but treatable conditions. Common adverse reactions, reported in at least 5% of patients receiving these drugs, included conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and increased intraocular pressure. These reactions are generally mild and temporary, resolving on their own or with minimal treatment.
For the treatment of Neovascular (Wet) Age-Related Macular Degeneration, the trials were conducted in 1824 patients who were treated the recommended dose in two double-masked, controlled clinical studies (VIEW1 and VIEW2). For Macular Edema, total of 309 patients were exposure to the drugs 6 months with a monthly 2 mg dose followed by central retinal vein occlusion in two clinical studies (COPERNICUS and GALILEO) and branch retinal vein occlusion (BRVO) in one clinical study (VIBRANT), in 218 and 91 patients respectively. Trial for Diabetic Macular Edema and Diabetic Retinopathy were conducted in 578 patients with DME were treated with the recommended dose in two double-masked, controlled clinical studies (VIVID and VISTA) from baseline to week 52 and from baseline to week 100. In all the studies less than 1% of patients were reported to develop adverse effect like corneal edema, retinal tear, hypersensitivity, and endophthalmitis.
Conclusion and Future Outlook
In conclusion, both biosimilars exhibit “no clinically meaningful differences from Eylea” [FDA report; May 2024]. The FDA approval of these biosimilars offers new hope for patients with Diabetic Retinopathy, providing affordable treatment options and potentially improving vision outcomes. Yesafili has already been approved in Europe and the UK in 2023 and is seeking a launch in Canada by July 2025.
Dr. Avraneel Paul, Ph.D.
Sources
- Daruich A, Matet A, Moulin A, et al. Mechanisms of macular edema: Beyond the surface. Prog Retin Eye Res. 2018;63:20-68.
- Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis (Lond). 2015;2:17.
- Rein DB, Wittenborn JS, Burke-Conte Z, Gulia R, Robalik T, Ehrlich JR, Lundeen EA, Flaxman AD. Prevalence of Age-Related Macular Degeneration in the United States in 2019. JAMA Ophthalmology. November 3, 2022
- Tranos PG, Wickremasinghe SS, Stangos NT, Topouzis F, Tsinopoulos I, Pavesio CE. Macular edema. Surv Ophthalmol. 2004 Sep-Oct;49(5):470-90.
- Virgili G, Parravano M, Evans JR, Gordon I, Lucenteforte E. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis. Cochrane Database Syst Rev. 2018;10:CD007419.
