The Reign of Keytruda: A Success Story in Immuno-Oncology
For the second consecutive year in 2024, Merck's Keytruda (pembrolizumab) topped the list of best-selling drugs worldwide, generating nearly $29.5 billion in sales. This monoclonal antibody, which works by blocking the PD-1 protein to help the immune system attack cancer cells, represents a new era in cancer treatment. Its success is not tied to a single use but is driven by its approval for over 40 indications across various cancers, including lung, melanoma, and cervical cancers. Merck has also been proactive in securing its future revenue, including developing a subcutaneous formulation to extend profitability even as key patents approach expiration.
Expanding Indications and Strategic Moves
Keytruda's robust sales growth is a testament to the expansion of its approved uses, extending its reach into new patient populations. For instance, a recent FDA approval for first-line treatment of pleural mesothelioma opened access to a market potentially exceeding $12 billion in value by 2034. The drug's success highlights a broader industry trend where highly specific, targeted therapies for complex diseases command premium pricing and massive revenues, often far outpacing traditional small-molecule drugs.
The Rising Tide of GLP-1 Therapies
While Keytruda has held the number one spot for individual products, the pharmaceutical landscape is undergoing a dramatic shift driven by GLP-1 agonists. These medications, originally for type 2 diabetes, have seen explosive demand for their weight-loss benefits. In the first quarter of 2025, the combined sales of Novo Nordisk's Semaglutide products (Ozempic for diabetes and Wegovy for weight loss) nearly reached $8 billion, collectively surpassing Keytruda's quarterly sales. Eli Lilly's Mounjaro (tirzepatide), which also treats diabetes and obesity (under the brand Zepbound), posted phenomenal growth as well, intensifying the competition.
The GLP-1 Battleground
The fierce competition between Novo Nordisk and Eli Lilly is a major storyline in the pharmaceutical industry. The high demand has caused supply constraints and led to aggressive moves for market share. In one instance, CVS Health removed Eli Lilly's Zepbound from its preferred formulary in favor of Novo Nordisk's Wegovy, signaling an intensifying price war. As more patients seek these therapies, the collective revenue of the GLP-1 class is on a trajectory to dominate the market.
From Reigning King to Market Decline: The Humira Story
For years, AbbVie's Humira (adalimumab) was the undisputed highest-selling drug in the world, treating a range of autoimmune and inflammatory diseases. However, its peak sales of over $21 billion in 2022 gave way to a rapid decline following the expiration of key patents in 2023. The entry of biosimilars—similar, lower-cost versions of the biologic drug—significantly eroded Humira's revenue. The decline illustrates the fragility of blockbuster status in the face of patent cliffs and robust biosimilar competition.
Key Factors Redefining the Pharmaceutical Market
The shifting dynamics at the top of the sales charts are not random. Several key factors influence what's the highest selling drug at any given time.
The Patent Cliff and Biosimilar Threat
Patent expirations trigger intense competition from biosimilars, which provide a safe, effective, and less expensive alternative to originator biologics. The severe revenue drop experienced by Humira after biosimilars entered the US market demonstrates the profound impact this can have on a blockbuster drug's sales. Biosimilar competition is also expected to affect Keytruda, whose main patents expire in 2028.
Pricing Pressure and Government Regulation
Rising drug costs have led to increased scrutiny and regulatory action. The US Inflation Reduction Act (IRA) allows for Medicare price negotiations on certain high-cost drugs, creating pricing pressure. Ozempic and Eliquis have both been selected for these negotiations, which could impact their future revenue. This pressure incentivizes pharmaceutical companies to find new areas of growth and innovation.
Innovation in Specialized Therapies
The high revenue generated by Keytruda and the GLP-1 drugs underscores the industry's focus on specialized therapies. These targeted treatments for complex conditions like cancer and metabolic disorders often have strong intellectual property protection and high price tags, making them incredibly profitable. The shift towards biologics and large molecules as the fastest-growing segment of the market reflects this trend.
Comparative Analysis of Top Blockbusters
To understand the shifts in the market, it's useful to compare the different eras of blockbuster dominance. The table below compares Keytruda, Ozempic, and the historical giant Humira.
| Feature | Keytruda (pembrolizumab) | Ozempic (semaglutide) | Humira (adalimumab) |
|---|---|---|---|
| Indication | Various cancers (immuno-oncology) | Type 2 diabetes (also widely used for weight loss) | Multiple autoimmune and inflammatory diseases |
| Approx. 2024 Sales | $29.5 billion | $16.9 billion | $9 billion |
| Market Trajectory | Peak sales approaching, facing biosimilar threat post-2028 | Explosive growth, intensifying competition from rivals | Rapid decline due to biosimilar competition |
| Drug Class | Monoclonal antibody (Biologic) | Glucagon-like peptide-1 (GLP-1) receptor agonist (Biologic) | Tumor necrosis factor (TNF) inhibitor (Biologic) |
| Primary Challenge | Future biosimilar competition and pricing pressure | Scaling manufacturing to meet demand, intense market competition | Protecting market share against biosimilars |
The Next Wave of Blockbusters
As the pharmaceutical landscape evolves, the race for the next highest-selling drug is well underway. While Keytruda continues to hold its ground, the growth of GLP-1 therapies points to a future where metabolic health treatments could dominate revenue charts. Other promising therapeutic areas are also emerging. The rise of new drugs in the oncology and autoimmune fields suggests a continued focus on specialized, high-value treatments. The industry continues to invest heavily in research and development, particularly in biologics and biosimilars, shaping the market for the next decade. According to Nova One Advisor, robust R&D investments are a hallmark of the US pharmaceutical market, which accounts for a significant portion of global sales and drives innovation.
Conclusion
The answer to "what's the highest selling drug" is a moving target, reflecting the constant evolution of medical science, market dynamics, and patient needs. The reign of Humira has ended, replaced by the immuno-oncology prowess of Keytruda, which itself faces challenges from the rapid rise of GLP-1 agonists. The pharmaceutical industry is in a state of flux, shaped by patent cycles, innovation, and pricing pressures. While specific drugs may rise and fall, the underlying trends point towards a future dominated by highly effective, targeted therapies for complex diseases, ensuring the competition for the top spot remains fierce.
