September 02, 2022
2 min read
September 02, 2022
2 min read
Lindstrom reports having financial disclosures for Alcon, Novartis and Ocular Therapeutix.
As discussed in my Aug. 25 commentary , biologics are poised to assume a major role in the treatment of patients with potential or actual vision loss from congenital or acquired eye diseases and ocular degenerations.
In review, a biologic is a therapeutic agent that is a living cell, is a component of a living cell such as a gene, or is produced by a living cell such as a secretome or protein. A biologic used in therapy is a biotherapeutic. FDA approval of biologics in the U.S. is under the direction of the Center for Biologics Evaluation and Research (CBER). Extensive data, including confirmatory positive results from two large prospective randomized masked clinical trials, are required to receive FDA CBER approval and launch a biologic commercially. The pathway to FDA approval is long and expensive.
Richard L. Lindstrom
The biotherapeutic agents we ophthalmologists are most familiar with are anti-VEGF proteins. These products are usually covered by extensive patent protection, just like the branded patent-protected drugs we use daily in our practices. When the patents protecting molecules approved as a drug expire, less expensive generic alternatives are manufactured, FDA approved and commercially launched at a lower price. A generic drug is required to be an identical version of the patented drug it is intended to replace.
For biologics, it is not possible to create an identical version because they are complex and created by living cells. This has resulted in the creation of a new class of biotherapeutics called biosimilars. A biosimilar is required to prove that it has a similar therapeutic effect as a previously FDA-approved biologic. There must be no clinically significant difference in biologic activity, safety and efficacy, but a biosimilar does not need to be identical like a generic drug. Biosimilars require extensive testing and at least a single large confirmatory FDA clinical trial to prove they produce similar outcomes and have similar safety and efficacy to the previously approved biologic. Like generic drugs, the development and regulatory costs are lower for biosimilars than new biologics, so they can be sold at a lower price and still be profitable.
In ophthalmology, biosimilars are about to have a significant impact on the anti-VEGF market. The branded, patented biotherapeutic anti-VEGF products such as Eylea (aflibercept, Regeneron) and Lucentis (ranibizumab, Genentech) are priced just under $2,000 a dose. This high price, the significant global patient need, a positive therapeutic index and the requirement for multiple annual injections have made anti-VEGF injections the most lucrative pharmaceutical product in ophthalmology. The average annual cost today to treat a single patient in the U.S. is $10,000 per eye, and the total global revenue generated by anti-VEGF products is just more than $12 billion per year. In the U.S., Medicare alone spends close to $3 billion per year on anti-VEGF therapy, and this cost represents 12% of the Medicare Part B budget. A therapeutically equivalent safe and effective biosimilar anti-VEGF will likely be priced at 25% to 35% of the currently available branded, patented biologic products. A transition from the patented biologics to a biosimilar will result in significant savings to the health care reimbursement systems in every country worldwide.
Like the transition from branded, patented drugs to generic drugs, increasing use of biosimilar alternatives to the proven branded anti-VEGF biotherapeutics used today will occur slowly and never reach 100% penetration. It will be interesting to watch the rate of biosimilar anti-VEGF adoption and the impact it has on branded anti-VEGF products and the off-label use of Avastin (bevacizumab, Genentech), which is priced at only $50 to $75 per injection. In the current payer environment, reduced cost per unit of care is highly valued, and this fact will drive increasing investment and development in the biosimilar category. Both biologics and biosimilars will become increasingly important as we ophthalmologists labor to preserve, restore and enhance vision.