Ophthalmology Biobetters and Biosimilars May Be Just Around the Corner

A strong push for the development and marketing of “biobetters” is anticipated, according to a review of biosimilar and new biologic development in ophthalmology.

The review, published in the International Journal of Retina and Vitreous, said that biobetters may require developers to make a larger investment in the development of biosimilars, but the odds of a biobetter reaching the production stage are very high.

Biobetters are similar to reference products but are chemically modified to have a different amino acid sequence or purification process, which can improve shelf life and pharmacological effects. On the other hand, biosimilars are considered highly similar to reference products because they have the same amino acid sequence and carry similar safety and efficacy profiles.

Examples of Emerging Biobetters

Susvimo, an ocular implant that administers ranibizumab injection into the eye and eliminates the need for intravitreal injections, is an example of a biobetter. The product, created by the same developer of the originator product, was approved by the FDA in October 2021 and will be used to treat neovascular age-related macular degeneration (wet AMD), macular edema, and diabetic retinopathy.

Ildong Pharmaceuticals, based in the Republic of Korea, is also developing a biobetter for patients being treated with ranibizumab that is hoped to improve efficacy and lessen resistance associated with the originator.

Upcoming Anti-VEGF Biosimilars

In addition to ranubizumab biobetters, other anti–vascular endothelial growth factor (VEGF) biosimilars are expected to come as well, including those for ranibizumab (Lucentis), bevacizumab (Avastin), and aflibercept (Eylea). However, aflibercept won’t be off patent in the United States until 2023.

Anti-VEGF drugs function by inhibiting the abnormal growth of blood vessels that can lead to subretinal bleeding and worsen vision. They are also used to treat diabetic macular edema and retinal vein occlusion.

The authors of the review found 10 manufacturers with ranbizumab biosimilars approved or in development, globally, including Samsung Bioepis’ Byooviz, which was approved in the United States and European Union in 2021, and Intas Pharmaceuticals’ Razumab, which was approved in India in 2015.

The Growing Number of Bevacizumab Biosimilars

Although reference bevacizumab is not indicated for ophthalmic conditions, it is commonly used off-label for the treatment of wet AMD because it is cheaper than ranibizumab. The authors said that the development of a bevacizumab biosimilar specifically for eye diseases could alter pricing dynamics.

In addition to the several bevacizumab biosimilars that have been approved and marketed in several markets around the world, Outlook Therapeutics is developing ONS-5010, which the FDA is currently reviewing in the form of an investigational new drug application. If approved, it will not be classified as a biosimilar. “If the intravitreal formulation is approved, the justification for the use of a compounded version [of bevacizumab] may no longer exist. However, it may lead to a paradoxical rise in the cost of bevacizumab in ophthalmology,” the authors wrote.

Aflibercept Biosimilars Under Development

The authors listed 8 aflibercept biosimilars that are under development, including those developed by Amgen, Formycon and Bioeq, Samsung Bioepis, Sandoz, and Celltrion Healthcare.

The authors also mentioned Alteogen’s aflibercept biosimilar formulation that is expected to improve the shelf life and heat resistance of the originator product.

The authors stressed that with the growing number of ophthalmology biosimilars expected to enter the market in the coming years, “pharmacovigilance, quality control, and monitoring are extremely important, along with immunogenicity testing before market approval.”

Reference

Kapur M, Nirula S, Naik MP. Future of anti-VEGF: biosimilars and biobetters. Int J Retin Vitr. 2022;9:2. doi:10.1186/s40942-021-00343-3