Tony Hagen is senior managing editor for The Center for Biosimilars®.
Multiple contenders are lining up for the pending expiration of patents on the blockbuster Regeneron reference product for wet age-related macular degeneration.
Among an increasingly crowded field for aflibercept biosimilar contenders, 2 Germany-based biosimilars companies have launched a phase 3 equivalence study for FYB203, an aflibercept candidate for the treatment of patients with neovascular age-related macular degeneration (nAMD).
The product was developed by Formycon, and in May, the company announced that the first regulatory approvals had been granted for the randomized, double-blind, multicenter trial comparing FYB203 with the reference product, Eylea, on the basis of efficacy, safety, and immunogenicity. Despite the coronavirus disease 2019 (COVID-19) pandemic, the enrollment phase of the trial is on schedule with the plans announced 3 months ago.
Formycon’s partner in this is Bioeq, a company with expertise in product management, clinical development, product administration systems, and licensing. Bioeq is sponsoring the phase III trial. Santo Holding, a Swiss company, holds the rights to global commercialization.
Potential Market Is Huge
nAMD, also known as wet AMD, is one of the main causes of loss of vision in people over the age of 50 in developed countries. Aflibercept inhibits vascular endothelial growth factor (VEGF), which is the cause of excessive formation of blood vessels in the retina and leads to progressive vision loss.
According to Formycon, Eylea is the top-selling drug in this market. The Regeneron product achieved revenues of $4.64 billion in 2019, up from $4.08 billion in 2018. As patents on Eylea have yet to run their course, there are no aflibercept biosimilars on the market in the United States or Europe. The product first topped $1 billion in quarterly sales in 2018.
According to Regeneron, the US and EU composition-of-matter patents on aflibercept will expire in 2023 and 2025, respectively. US manufacturing, formulation, and administration regimen patents on Eylea expire in 2026, 2027, and 2032, respectively, and formulation patents in the European Union expire in 2027. Regeneron has indicated that it may attempt to extend product exclusivity for Eylea by filing additional product claims. The drug loses its patent protection in China and Japan in 2022.
Aflibercept was approved for wet AMD by the FDA in 2011. It subsequently received additional indications for diabetic macular edema (DME) and diabetic retinopathy in patients with DME. Most recently, the FDA approved Eylea injection for diabetic retinopathy and a prefilled syringe product containing aflibercept. The prefilled syringe product was launched in the United States in December 2019. It was approved by the European Medicines Agency (EMA) in April 2020.
In a statement, Formycon and Bioeq explained that the FYB203 study has been designed in accord with the FDA, EMA, and the Japanese Pharmaceuticals and Medical Devices Agency.
“We are delighted that our second project in the field of ophthalmology is now starting the phase 3 study,” Stephan Glombitza, chief operating officer of Formycon, said in a statement. “Given the extensive experience from the FYB201 project and the successful cooperation with Bioeq GmbH, we are confident that we will also be able to develop a high-quality and cost-effective biosimilar with FYB203.”
Other biosimilar developers that are positioning to enter the aflibercept market are Momenta Pharmaceuticals (M710), Altogen (ALT-L9), and Amgen, which began a phase 3 trial for ABP 938 earlier this year. Also, Coherus BioSciences has an aflibercept biosimilar (CHS-2020) in pre-clinical development. Samsung Bioepis also seeks to enter this market with SB15. The company recently announced the start of a phase 3 clinical trial.