Osteoporosis drug Prolia faces intense competition as patents expire and generics launch

Last year, the osteoporosis treatment drug Prolia (denosumab) generated revenue of 9 trillion won globally, and its patent has sequentially expired in major countries since last month, intensifying competition for biosimilars. With U.S. Sandoz being the first to enter the local market, domestic corporations are also planning to launch their products one after another. However, as Amgen, a major revenue source for Prolia, is engaged in patent disputes with biosimilar developers to extend its monopoly period, negotiations with Amgen appear to be key for market entry.

According to the industry on the 20th, the patent for Prolia, developed by U.S. Amgen, expired in February in the U.S., is set to expire this month in South Korea, and will expire in Europe in November. Domestic and international biosimilar developers are already developing products and obtaining approvals in preparation for market entry.

Launched in 2010, Prolia reduces bone destruction by blocking the cell membrane protein (RANKL) that activates osteoclasts and increases bone mass and strength. Prolia has also been proven effective in preventing complications from bone metastases in cancer patients during its first year of launch and received approval under the name Xgeva.

The two products generated $1.22 billion (1.78 trillion won) in revenue within two years, earning blockbuster status. Last year, the combined global revenue of Prolia and Xgeva reached $6.599 billion (9.2 trillion won), making it the best-selling drug among all of Amgen's products.

Swiss Sandoz was the first to announce its entry into the U.S. market. In March last year, the company's biosimilar products Jubbonti and Wyost, developed for Prolia and Xgeva, were the first to receive approval from the U.S. Food and Drug Administration (FDA). They have the same formulation and administration method as Prolia and Xgeva, and can be substituted for all conditions the original drugs treat. They are expected to be sold in the U.S. market as early as the end of May.

Domestic bio corporations are also preparing for market entry by obtaining FDA approval one after another. In particular, as Celltrion and Samsung Bioepis, the two giants in the domestic biosimilar industry, are rushing to develop products, intense competition is expected in the bone treatment market, following the autoimmune disease treatment market.

Celltrion received FDA approval in February for its biosimilars Stoboclo and Osenvelt, which target Prolia and Xgeva. Stoboclo is approved for postmenopausal osteoporosis in women, and Osenvelt is approved for the prevention of skeletal complications in cancer patients with bone metastasis, receiving approval for all conditions treated by the original Prolia and Xgeva in the U.S.

Samsung Bioepis also received product approval in February for its biosimilars Ospomyv and Xbryk related to Prolia and Xgeva in the U.S., and received approval in Europe under the names Obodence and Xbryk. These products can also be used for all conditions treated by Prolia and Xgeva.

Additionally, U.S. Odonon, the Chinese Shanghai Henlius Biotech alliance, Israel Teva, and Germany Fresenius Kabi are preparing to launch Prolia biosimilar products.

Although Celltrion and Samsung Bioepis have received approvals for Prolia and Xgeva biosimilars in the U.S. and Europe, they are not immediately able to enter the market due to ongoing legal hurdles from Amgen's patent infringement lawsuits.

The more a drug is a blockbuster, the more often the original drug developer tries to monopolize revenues by obstructing the market entry of biosimilar developers. Once a biosimilar hits the market, the original drug's sales decline due to price competition. Therefore, it’s common for the original drug developer approaching the patent expiration to engage in patent infringement lawsuits to delay biosimilar launches.

Amgen also moved quickly two years before the patent expiration. In May 2023, it filed a patent infringement lawsuit against Sandoz, which was conducting clinical trials for its Prolia biosimilar. This was followed by consecutive patent lawsuits against Celltrion in May last year and Samsung Bioepis in August.

To ensure the products are released as scheduled and establish themselves in the local market, resolving patent dispute risks with the original pharmaceutical companies is crucial. Sandoz was able to launch on May 31 after negotiating with Amgen after about a year of dispute last April. Celltrion is also reported to be able to launch in the U.S. starting in June through a patent agreement with Amgen. However, specific details of the negotiations or the launch timing have not been disclosed.

Samsung Bioepis is still engaged in a patent dispute with Amgen. Following Amgen's patent infringement lawsuit against biosimilars, which was filed in the commercial court in Brussels, Belgium, being dismissed last December, there are analyses that Samsung Bioepis may gain an advantageous position in future patent negotiations with Amgen.

A source in the industry noted, "Patent lawsuits are a common occurrence for biosimilar developers, so the case of Prolia is not a new story," adding, "In a situation where the competitiveness of domestically produced biosimilars is increasing, it is also important for each party to establish a patent avoidance strategy to prevent disruptions in their business."