One of two biologics injected intravitreally to treat forms of macular degeneration, edema, or retinopathy, Eylea® (aflibercept) was first approved by the US Food and Drug Administration (FDA) on November 18, 2011. Originally approved as a single-dose vial, its manufacturer, Regeneron, received FDA approval of a prefilled syringe in December 2019. We covered the potential biosimilar competitors for the second product, Lucentis® (ranibizumab), in January 2020.
Eylea has significantly greater sales (and growing) than Lucentis. Regeneron reported Q4 2019 US revenues for the innovator product Eylea at $1.22 billion, which represented a 14% increase over the same quarter of 2018. Total US sales for 2019 were $4.64 billion. In its most recently reported quarter (Q2 2020), sales slipped to $1.114 billion, but this was likely attributable to the COVID-19 outbreak discouraging physician office visits. In comparison, Lucentis sales are roughly a quarter of this figure.
Aflibercept belongs to the class of vascular endothelial growth factor agents, and there are two forms currently prescribed. Eylea is indicated for ophthalmologic uses only. Zaltrap® (also known as ziv-aflibercept) was approved for use as an intravenous infusion for oncology patients to address specific cancer mutations. Regeneron and partner Sanofi Genzyme own the rights to Zaltrap.
Several aflibercept biosimilar candidates are in development, hoping to market after the 2020 US patent expiration. The following is a summary of the publicly disclosed players.
AFLIBERCEPT BIOSIMILAR CANDIDATES
|Company Name||Drug Name||Possible FDA Submission Dates|
|Samsung Bioepis||SB15||Q1 2022|
|Amgen||ABP 938||Q1-Q2 2022|
Mylan. MYL-1701P (also referred to as M710, as part of a partnership with Momenta Pharmaceuticals) is perhaps the aflibercept biosimilar that is furthest along in the development process. It is currently the subject of a 324-patient phase 3 trial. The patients in this study, which started in 2018 and is scheduled to be completed in December 2020, have diabetes-related macular edema. Earlier this month, Momenta was acquired by Johnson & Johnson, and M710 was the sole biosimilar remaining in its portfolio. Mylan is to handle development and commercialization. Mylan believes that it will file a 351(k) submission by early 2021, which could mean an FDA decision in early Q1 2022.
Samsung Bioepis. SB15 is an aflibercept biosimilar candidate that began a phase 3 trial on June 23, 2020. The recruitment objective is 446 participants with neovascular age-related macular degeneration, with a scheduled completion date of February 2022 (primary completion date of March 2021). Samsung completed its phase 3 trial of its Lucentis biosimilar SB11 in December 2019, which is interesting, because of the direct competition between the Lucentis and Eylea brands.
Amgen. ABP 938 is Amgen’s aflibercept biosimilar candidate. A phase 3 trial of this agent began in June 2020, comparing ABP 938 with US-licensed Eylea in 566 patients with neovascular age-related macular degeneration. The study is scheduled to conclude in July 2022, with primary results reported in September 2021.
Alteogen We first reported on theSouth Korean company Alteogen in January 2018, when it had completed preclinical testing on the investigational aflibercept biosimilar ALT-L9. The phase I trial for this aflibercept biosimilar was slated to begin October 2019 in patients with patients with neovascular age-related macular degeneration. The completion date is December 2020.
Formycon. Bioeq GmbH is responsible for managing Formycon’s pharmaceutical development program for its aflibercept biosimilar FYB203. Bioeq began a phase 3 trial on July 23, 2020 to compare FYB203 to Eylea in 400 patients with neovascular, age-related macular degeneration. With a primary completion date of August 2021, this should enable Formycon to file an application with the EMA in 2025 and/or the FDA sometime in 2022 and potential US introduction in 2023.
Coherus Biosciences. Coherus BioSciences, the maker of the pegfilgrastim biosimilar Udenyca®, is still in the preclinical development stage with its aflibercept biosimilar candidate CHS-2020. According to Coherus, clinical trials for this biosimilar is slated to begin in 2021. Based on this timeline, FDA submission may not occur until the 2024 timeframe, which could make Coherus one of the late arrivals to market.