The standing of Eylea (aflibercept), which has monopolized the macular degeneration drug market for more than 10 years, is wobbling. As biosimilars enter the market in earnest and next-generation new drugs with novel treatment modalities roll out one after another, a rapid shake-up of the market is expected.
Macular degeneration is a disease in which the macula, the central area of the retina where photoreceptors are concentrated, is damaged by aging, causing vision to deteriorate rapidly. In severe cases, it can lead to blindness. According to market research firm Grand View Research, the global macular degeneration drug market is projected to reach $13.2 billion (18 trillion won) in 2028, up from $9.84 billion (13 trillion won) in 2021.
◇"Stop Eylea's solo run"… next-generation new drugs emerge one after another
Eylea, co-developed by U.S. Regeneron and Germany's Bayer, has held the No. 1 spot in the macular degeneration drug market for more than 10 years since its 2011 launch. Last year's global sales reached 13.6 trillion won. But Roche's new drug Vabysmo won U.S. Food and Drug Administration (FDA) approval in 2022 and has been rapidly expanding its share, shaking up the market landscape.
While Eylea targets only vascular endothelial growth factor (VEGF), which induces the formation of abnormal new blood vessels harmful to vision, Vabysmo enhances efficacy as a bispecific antibody that simultaneously blocks VEGF and angiopoietin-2 (Ang-2), which causes instability in new blood vessels and increases vascular leakage.
According to pharmaceutical market research firm Market Scope, in the second quarter of this year Eylea's sales were $2.1 billion (3 trillion won), down 13% from a year earlier, while Vabysmo posted $1.3 billion (1.86 trillion won), up 19% year over year.
Recently, U.S. Eli Lilly also entered the ophthalmology market by acquiring gene therapy developer Adverum for about 100 billion won. Adverum has a macular degeneration gene therapy candidate called ixo-vec.
Existing gene therapies are administered under the retina via surgery, but ixo-vec can be injected into the vitreous, the jelly-like area behind the lens. It is designed to continuously maintain intraocular aflibercept concentrations with a single injection. It has also been designated for priority review by the FDA and the European Medicines Agency (EMA).
New drug development is active in Korea as well. OliX Pharmaceuticals is conducting a phase 2a clinical trial for treatments not only for wet macular degeneration but also for dry eye disease, and is discussing technology transfer with a global pharmaceutical company. AptaBio is conducting a phase 1 trial of an oral macular degeneration treatment, and REYON Pharmaceutical is conducting a phase 1/2a trial of NG101, a wet macular degeneration gene therapy, with Neuracle Genetics.
◇Biosimilars race on timing for U.S. market launch
Not only new drugs but also biosimilars that copy Eylea are shaking Eylea's position. Eylea's compound patent expired in the United States in June last year and in Europe in May this year. Domestic and overseas companies are accelerating biosimilar launches backed by price competitiveness.
To extend its patent rights, Regeneron filed formulation and process-related patent lawsuits in the United States against biosimilar developers. As 60% of Eylea's total sales come from the U.S. market, the intent is to block biosimilar entries and extend exclusivity. The corporations sued include Sandoz, Amgen, and Mylan, as well as domestic companies Celltrion and Samsung Bioepis.
Amgen, the only company to have won in litigation so far, plans to launch Pavblu, an Eylea biosimilar, in the United States next year. Mylan, which reached a settlement with Regeneron, will launch in the second half of next year, and Celltrion will enter the U.S. market at the end of next year. Early this month, Celltrion won FDA approval for Eydenzelt, an Eylea biosimilar.
Samsung Bioepis received FDA approval in May this year for Ophuviz, an Eylea biosimilar, but has yet to reach a settlement with Regeneron, so the timing of its U.S. market entry is undetermined. In Korea, Eylea's compound patent expired in Jan. 2023, and both Celltrion and Samsung Bioepis launched biosimilars. Samsung Bioepis is also preparing to enter the European market.
An industry official said, "The price competitiveness of biosimilars and new drugs, including gene therapies, will shake the market at the same time," adding, "the next two to three years will be a watershed for the macular degeneration drug market."