Understanding the Shift: What is the top selling drug in America? (2024-2025)

October 8, 2025 •

4 min read

According to data from 2024, Merck's cancer drug Keytruda has claimed the top spot in global pharmaceutical sales, showcasing a significant shift in the market after years of AbbVie's Humira leading the pack. For those asking, 'What is the top selling drug in America?', the answer has become more complex, reflecting major changes driven by biosimilar competition, new drug classes, and shifting patient needs.

Quick Summary

The top-selling drug in the U.S. has changed, moving away from the long-standing leader Humira. This shift was caused by patent expirations and biosimilar competition, allowing new drugs like Keytruda and Ozempic to rise based on robust sales.

Key Points

End of an Era: AbbVie's Humira, the long-time best-selling drug, has been displaced from the top spot due to patent expiration and market competition from biosimilars.
New Leader: Merck's cancer drug, Keytruda, has taken the lead in global pharmaceutical sales, driven by its success in treating numerous cancer types.
Surging Contender: Novo Nordisk's Ozempic, a GLP-1 agonist for diabetes and weight loss, has seen explosive sales growth and is a major challenger for the top revenue spot.
Biosimilar Impact: Competition from lower-cost biosimilars is a critical factor influencing revenue, as demonstrated by the significant decline in Humira's sales following the entry of generic versions.
Market Diversification: The shift indicates a move away from single-drug dominance, with strong performances also coming from other areas like Eliquis (anticoagulant) and Dupixent (immunology).
Regulatory Influence: Future market dynamics will be shaped by factors such as government drug price negotiations under the Inflation Reduction Act, which targets high-cost medications.

The End of an Era: Humira's Reign Concludes

For nearly two decades, AbbVie's Humira (adalimumab) was an untouchable titan in the pharmaceutical industry, consistently ranking as the world's best-selling drug. Used to treat a range of inflammatory conditions like rheumatoid arthritis and Crohn's disease, Humira generated billions in revenue annually, peaking at over $21 billion globally in 2022. AbbVie successfully defended its market exclusivity for years through a complex web of patents, delaying the entry of lower-cost biosimilars. However, this dominance began to crumble when the primary patent expired, allowing biosimilars to enter the U.S. market starting in 2023. By 2024, the intense biosimilar competition had caused Humira's sales to plummet, pushing it out of the top ten list for the first time in years.

The New Market Leaders

With Humira's fall, several other drugs stepped up to fill the vacuum, representing a diversification of market dominance across different therapeutic areas. The new leaders include a powerful immuno-oncology treatment, a popular diabetes and weight-loss medication, and a widely used anticoagulant.

Keytruda: The Cancer Blockbuster

Leading the charge is Merck's Keytruda (pembrolizumab), a breakthrough cancer immunotherapy. Keytruda works by helping the body's immune system detect and fight cancer cells and has seen its sales skyrocket due to its approval for over 40 cancer indications. In 2024, Keytruda cemented its position as the top-selling drug globally, with sales approaching $30 billion. Its continued expansion into new indications, though facing a looming patent expiration in 2028, makes it a formidable force in the market.

Ozempic and the Rise of GLP-1s

Another major market mover is Novo Nordisk's Ozempic (semaglutide), a GLP-1 receptor agonist originally approved for type 2 diabetes. The drug, and its companion weight-loss version Wegovy, have experienced explosive growth, fueled by high demand and broad media attention. The rise of GLP-1 drugs signifies a new paradigm in pharmaceuticals, with huge revenue potential in treating widespread metabolic conditions like diabetes and obesity. For example, in 2023, semaglutide topped U.S. spending lists, and its growth continued strongly into 2024. The sales surge, however, faces challenges from competitors like Eli Lilly's Mounjaro and potential impacts from government drug price negotiations under the Inflation Reduction Act.

Factors Reshaping the Pharmaceutical Landscape

The shift in the top-selling drug reflects broader trends transforming the pharmaceutical industry.

The Impact of Biosimilars

The arrival of biosimilars has profoundly impacted drug revenues, particularly for biologics like Humira. Once market exclusivity ends, biosimilars introduce competition that drives prices down and reshuffles market share. While uptake can be gradual, as seen initially with Humira's biosimilars, it inevitably erodes the branded drug's dominance. This trend is expected to continue with other high-revenue drugs as their patents expire, including Keytruda later this decade.

Government Regulation

Legislation such as the Inflation Reduction Act (IRA) is also playing a role by enabling Medicare to negotiate prices for certain high-cost drugs. Eliquis and Jardiance, both top revenue generators, were among the first group selected for negotiations, with final maximum fair prices set to take effect in 2026. This policy adds another layer of complexity for pharmaceutical companies, requiring them to factor potential revenue reductions into their market strategies.

Emerging Drug Classes

The phenomenal success of GLP-1 agonists highlights the industry's focus on innovative drug classes targeting common, widespread health issues. The market for obesity treatments alone is projected to grow significantly, offering huge opportunities for companies that can deliver effective therapies. This trend contrasts with the previous dominance of specific immunology or cancer drugs, suggesting a move toward addressing broader population health needs with new pharmacological solutions.

Comparison of Past and Present Market Leaders


Feature	Humira (Past Leader)	Keytruda (Current Leader)	Ozempic (Rising Star)
Manufacturer	AbbVie	Merck & Co.	Novo Nordisk
Sales (2024 Est.)	~ $9 billion (declining)	~ $29.5 billion	~ $18.7 billion
Therapeutic Area	Immunology (autoimmune diseases)	Oncology (cancer immunotherapy)	Diabetes & Weight Loss (GLP-1 agonist)
Patent Status	Lost U.S. exclusivity in 2023, facing biosimilar competition	Key patents expire in 2028	U.S. patent expires in 2032
Primary Mechanism	Tumor necrosis factor (TNF) blocker	Programmed death-1 (PD-1) inhibitor	Glucagon-like peptide-1 (GLP-1) receptor agonist

The Evolving Landscape

The pharmaceutical market is in constant flux, driven by scientific innovation, regulatory changes, and competitive pressures. While Keytruda currently leads in total sales, the rapid growth of Ozempic and other GLP-1 drugs demonstrates that the top position is not guaranteed for long. Companies like AbbVie are already shifting their focus to next-generation therapies like Skyrizi to offset lost Humira revenue, further illustrating the dynamic nature of the market.

Conclusion In conclusion, the answer to what is the top selling drug in America and globally has changed dramatically. The long-time leader, Humira, has been eclipsed due to biosimilar competition. Merck's Keytruda has emerged as the new revenue leader, while Novo Nordisk's Ozempic is experiencing explosive growth, particularly in the U.S. market. These shifts are emblematic of a broader transformation within the pharmaceutical industry, highlighting the impact of patent expirations, emerging drug classes, and regulatory actions. The future top-seller is anyone's guess, but the trends suggest continued competition and innovation across oncology, metabolic disorders, and beyond.

The Future of Drug Development

The landscape of pharmaceutical sales and development is constantly changing, driven by factors beyond individual drug performance. Companies are now investing heavily in new research areas and technologies, aiming to find the next generation of blockbusters. The use of AI in drug discovery, for instance, is a growing area of focus for major players like Novo Nordisk, which invested in an AI supercomputer in collaboration with Nvidia. This technological push, alongside the maturation of key drug portfolios, indicates a future where therapeutic advances are accelerated, and market leadership remains in constant motion.

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Frequently Asked Questions

Humira lost its decades-long top spot primarily due to the expiration of its patent protection. This allowed competing, lower-cost biosimilars to enter the market starting in 2023, significantly eroding Humira's sales and market share.

Keytruda is a cancer immunotherapy drug used to treat a wide range of cancers, including various types of lung, skin, and gynecological cancers.

Both Ozempic and Wegovy contain the active ingredient semaglutide. The key difference is their FDA-approved use: Ozempic is for managing type 2 diabetes, while Wegovy is specifically approved for chronic weight management.

Biosimilars are generic versions of complex biologic medications like Humira. They have the same clinical effect but are often sold at a lower cost. Their entry increases competition and drives down the price and revenue of the original brand-name drug.

Under the Inflation Reduction Act, Medicare is empowered to negotiate prices for certain high-cost drugs. This process can significantly reduce the price and revenue for the affected drugs, potentially altering their top-selling status over time.

The 'top-selling drug' is typically determined by total revenue. While generic drugs like atorvastatin (a cholesterol medication) receive a very high number of prescriptions due to their low cost, their total revenue is often less than that of high-priced, specialty medications.

When a top-selling drug loses patent protection, the manufacturer typically experiences a significant decrease in revenue. Companies often prepare for this by focusing on new drug development or expanding sales of other existing products to compensate for the lost income.