The San Diego View

For this month’s Retina Corner, I wanted to discuss something that we will be hearing more and more about over the coming years, biosimilars. Most people are familiar with the concept of generic drugs but not biosimilars. Once a drug’s patent runs out, other companies can create a structurally and functionally similar product to compete with the original. Generic drugs are small molecules, relatively simple to duplicate and manufacture. Biologic drugs are 100 to 1,000 times larger than generics and are made up of hundreds of amino acids biochemically designed in a particular sequence within a living cellular system.

When people think of biologic agents they more commonly think of the world of oncology or rheumatology. So how does this apply to the field of retina? Well, we use a significant number of biologic drugs on a regular basis. In fact, more than 6 million intravitreal injections were completed in the U.S. alone last year. The current FDA approved intravitreal biologic anti-VEGF agents include Lucentis (ranibizumab), Eylea (aflibercept), Beovu (brolucizumab), and most recently Vabysmo (faricimab). Avastin (bevacizumab) is not FDA approved for intraocular use but is very commonly used off label. Given the significant demand for these drugs and original patents for ranibizumab and aflibercept expiring, there was an opportunity for other companies to develop a competing product.

The average original biologic costs $1.2 billion to $2.5 billion (in U.S. dollars) and takes roughly 10 to 15 years to develop. In contrast, research and development (R&D) for a biosimilar takes eight to 12 years—and costs $100 million to $200 million. Biosimilar companies argue that the existing treatment options are a cause of significant financial burden on the healthcare system and that there is a need for cheaper alternatives. They are also eager to carve out a piece of this highly profitable sector for themselves and their investors. However, there are detractors of the biosimilar movement. They argue biosimilars are dangerous and pose risks to patients. This is because the regulatory requirements for FDA approval of biosimilars are far less rigorous than the original biologics. Biosimilar drugs aren’t required to be put through phase 1 or 2 clinical trials with years of follow-up data. Companies do not have to prove superiority to existing drugs, just equivalency. Additionally, once proven effective, a biosimilar can be approved for all the indications of its original biological medication. For example, while Eylea (aflibercept) was required to do separate multi-phase, multi-year, large scale clinical trials for age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), and retinal vein occlusion (RVO), a biosimilar just has to show equivalency in a single phase 3 trial for one of these indications and receives blanket coverage for all others.

In 2022, we had the first FDA approved biosimilars in retina, Byooviz and Cimerli. These were both designed based off ranibizumab. At a price point of $1,130 for a single-use 0.5-mg vial, Byooviz offers an almost 40% discount to the current list price for Lucentis. The company has been aggressively marketing the drug and we may start to see widespread use in 2023. With numerous other biologics in development, we may soon have a plethora of drugs in what was very recently a market with few options. It will be important to watch outcomes and safety profiles closely as these drugs are widely used for the first time. Whatever the real motivation behind these products may be, the transition to biosimilars could make a substantial impact all over the world. They have proven to be useful in the fields of oncology and rheumatology, hopefully the same will be true in the field of ophthalmology.

I hope you enjoyed this month’s edition of Retina Corner! If you have any questions or if there is ever anything I can help with, please feel free to contact me at any time.

Best wishes, and until next time,
Mike

Michael Ammar, MD
Retina Consultants San Diego
480-323-9196 (cell)
ammar@rcsd.com