A Pioneering RANKL-Targeted Therapy with a Dominant Market Position

Amgen's Prolia and Xgeva are leading monoclonal antibody therapies that target RANKL (RANK ligand) to control osteoclast activation. Approved under FDA BLA 125320, denosumab, the active ingredient, initially entered the market in June 2010 as a treatment for osteoporosis. Subsequently, the higher-dose formulation, Xgeva, received approval for the prevention of skeletal-related events (SREs), further solidifying Amgen's leading position in the bone disease market. These drugs have maintained a strong standard of care in the treatment of bone diseases due to their proven clinical efficacy.

A Multi-Billion Dollar Revenue Stream

The denosumab franchise has been a key financial driver for Amgen's long-term growth. In 2024, Prolia achieved global annual sales of approximately $4.37 billion, demonstrating robust growth of 8% year-over-year. Combined with Xgeva's 2024 sales of approximately $2.1 billion, the total denosumab revenue reached approximately $6.5 billion, representing a significant portion of Amgen's overall revenue. This substantial cash flow has enabled Amgen to aggressively pursue subsequent biosimilar R&D and mergers and acquisitions (M&A).

The Impact of Biosimilar Competition and Patent Settlements

However, with the expiration of its exclusivity period, a wave of biosimilar competition from global pharmaceutical companies has begun. In March 2024, Sandoz received approval for its first interchangeable biosimilars, Jubbonti and Wyost, and, in accordance with patent settlement agreements, launched them in the U.S. market on June 2, 2025. Subsequently, in March 2026, Samsung Bioepis and Organon's Ponlimsi received FDA approval, and other competitors continue to emerge. The increasing market penetration of these biosimilars is disrupting Amgen's previously dominant market position.

Interchangeability Designation Fuels Price Erosion

In particular, the interchangeable designation, which allows for pharmacist-level substitution at the pharmacy, is directly impacting Amgen's ability to defend its market share. The shift in prescriptions from the originator product to biosimilars, without physician intervention, is accelerating, making a decline in Amgen's market share inevitable. Amgen is also striving to protect its market share through price discounts and rebates, but this inevitably leads to a decline in net prices and reduced profit margins. Ultimately, the price pressure resulting from patent expiration is fundamentally changing the competitive landscape of the osteoporosis drug market.

Amgen's Challenges in Preparing for the Post-Denosumab Era

To overcome this patent cliff, market attention is now focused on Amgen's post-denosumab strategy. Amgen is expanding the use of its other bone disease treatment, Evenity, and is accelerating the clinical development of Tezspire for asthma and MariTide, a potential obesity drug. Investors and job seekers should carefully compare the level of sales erosion of existing products with the market adoption rate of next-generation pipeline products. The successful transition of the portfolio will be a key factor in determining Amgen's medium- to long-term value.