The pharmaceutical landscape witnessed a monumental shift in 2004 when Pfizer's Lipitor broke through the $10 billion sales mark, becoming the first drug in history to achieve this milestoneThis watershed moment opened the floodgates for other blockbuster drugs, with AbbVie’s Humira emerging as the second drug to reach the illustrious billion-dollar club by 2013. Two decades later, the number of drugs that have crossed the threshold into the “billion-dollar club” has increased significantly.

According to financial reports from multinational pharmaceutical companies for 2024, a remarkable eleven drugs surpassed $10 billion in sales in the previous year aloneWith potential contenders like Vertex Pharmaceuticals' Trikafta gaining momentum, the annual total for the billion-dollar club is poised to reach twelveThe financial reports also highlight the robust growth of several candidate drugs, indicating that this number is likely to expand further in the future.

As these blockbuster drugs continue to define the market, the rankings of the world's top ten pharmaceutical companies have gone through a transformationEli Lilly has secured the ninth position with Tirzepatide, while GlaxoSmithKline has fallen off the listInstitutions predict that by 2030, the global market for anti-obesity drugs could reach a staggering $100 billionWith the soaring sales of Semaglutide and Tirzepatide, the landscape of leading drugs in 2025 remains shrouded in uncertainty.

The “billion-dollar club” is not just a badge of honor; it represents the pinnacle of success in the pharmaceutical industryIn recent years, the bar for entering this elite group has risen to $10 billion annually, a jump from the previous $1 billion benchmark for significant drugsA compilation reveals that 19 drugs have achieved over $10 billion in sales throughout history.

Among the ten blockbuster drugs that reached this milestone in 2023 are Keytruda, Semaglutide, Humira, Apixaban (Eliquis), Biktarvy, Dupixent, the COVID-19 vaccine Comirnaty, Ustekinumab (Stelara), Empagliflozin (Jardiance), and Nivolumab (Opdivo).

In 2024, the number of billion-dollar drugs once more hit an all-time high, but the collection of drugs has changed dramatically

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While Humira and Comirnaty saw their sales dip below the billion-dollar mark over the past year, AbbVie’s Skyrizi, Lilly’s Tirzepatide Mounjaro, and Johnson & Johnson’s Darzalex propelled the roster of the “billion-dollar club” to new heights.

Keytruda and Semaglutide have both seen explosive growth, collectively inching toward the $30 billion mark in salesKeytruda reported an impressive $29.48 billion in revenue, an increase of 18%, while the Semaglutide series surged by 38.43%, achieving $29.30 billion in sales.

Notably, drugs like Eliquis and Dupixent maintained their billion-dollar status, with Eliquis netting $20.70 billionMeanwhile, Dupixent saw sales reach $14.79 billion, marking a growth rate of 23.10%. Gilead’s Biktarvy reported sales of $13.42 billion, capturing half of the market share in the United States.

As we reached press time, the rankings were still in fluxBoth Opdivo and Jardiance are projected to retain their billion-dollar records for the entire year, and Vertex Pharmaceuticals’ Trikafta has already achieved $7.52 billion in sales within the first three quarters of this year, on track to join the billion-dollar club, potentially bringing the total roster to twelve.

Nonetheless, AbbVie’s former star, Humira, and Pfizer and BioNTech's COVID-19 vaccine Comirnaty both fell below the billion-dollar threshold in sales over the past year.

The quest for the next pharmaceutical king remains uncertainSince Lipitor, the pharmaceutical crown has transitioned to its fourth generation, with the highest record held by Pfizer’s COVID-19 vaccine Comirnaty at $40.34 billionWith the meteoric rise of GLP-1 medications led by Semaglutide, there is a strong possibility that this record may soon be eclipsed.

Behind this rapid rise in sales is a massive global market fueled by clinical demand

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Keytruda has continuously expanded its indications and administration methods, pushing sales boundaries, while GLP-1 medications represent a multi-billion-dollar market for glucose control and weight management.

Developed by Merck, Keytruda is a PD-1 inhibitor that received approval for its 40th indication in the U.S. in June 2024, covering multiple cancers such as lung cancer, head and neck cancer, esophageal squamous cell carcinoma, melanoma, colorectal cancer, gastric cancer, liver cancer, and triple-negative breast cancer.

In November 2024, Keytruda's subcutaneous formulation successfully advanced to Phase III trials, shortening the average administration time to just 2-3 minutes compared to intravenous administration.

Despite these achievements, there remains uncertainty about whether Keytruda can retain its title as the reigning king of pharmaceuticals in 2025. Semaglutide, initially approved as a diabetes treatment by the FDA in 2017, has gained tremendous momentum, surpassing $10 billion in sales in 2022 and breaking the $20 billion mark in 2023. By 2024, Novo Nordisk’s Semaglutide series (which includes the diabetes version Ozempic, oral version Rybelsus, and weight-loss version Wegovy) achieved a total sales of $29.30 billion, just $2 billion shy of the leading drug.

Semaglutide has shown remarkable growth and has a serious chance of claiming the new pharmaceutical crown by 2025.

With applications expanding from diabetes management to weight loss, Semaglutide's indications are continuously broadeningIn January of this year, Novo Nordisk announced that the FDA approved Ozempic for reducing the risk of kidney disease progression, kidney failure, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease (CKD). This signifies that GLP-1 medications are breaking into the realm of comprehensive management of diabetic kidney disease.

Lilly’s Tirzepatide, Semaglutide's primary competitor, also harbors immense potential

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The diabetes version Mounjaro achieved explosive growth of 124% in sales, crossing the billion-dollar mark in 2024, while the weight-loss version Zepbound generated nearly $4.93 billion in sales.

The application indications for Tirzepatide continue to expandOn December 20, 2024, the FDA granted new indications for Zepbound, specifically for obstructive sleep apnea (OSA). Additionally, Lilly has submitted an application to the regulatory agency for Tirzepatide to treat heart failure with preserved ejection fraction.

Both Lilly and Novo Nordisk are investing heavily to increase production capacityNovo Nordisk committed $4.1 billion in 2024 to build facilities to expand Semaglutide supply, while Lilly expects the market-ready dosage of GLP-1 drugs in the first half of 2025 to be at least 1.6 times that of the first half of 2024.

As the production capacities for Semaglutide and Tirzepatide expand, the ceiling for the next pharmaceutical king will likely be pushed even higher in 2025.

In this dynamic market, significant sales growth has reshuffled the rankings of prominent pharmaceutical companiesPresent financial reports indicate that the combined revenue of the world's top ten pharmaceutical firms reached approximately $584.1 billion, with Johnson & Johnson leading with $88.8 billion in total revenue, followed by Roche and Merck in second and third places, respectively.

Johnson & Johnson’s Stelara, despite facing the influx of biosimilars and a 4.6% year-over-year revenue decline, managed to maintain its position in the billion-dollar club with an annual revenue of $10.36 billionMeanwhile, Darzalex, a targeted treatment for multiple myeloma, crossed the $10 billion threshold for the first time, achieving annual revenue of $11.67 billion, a 19.8% increase.

With these accomplishments, Johnson & Johnson found itself as the only company in 2024 with two billion-dollar drugs.

From Lipitor for cholesterol management to healthy COVID-19 vaccines like Comirnaty and treatments like Paxlovid, Pfizer holds four positions on the list of 19 drugs that have achieved billion-dollar status in history

Pfizer's total revenue for 2024 reached $63.63 billion, reflecting a 7% increase.

In terms of revenue generated by Eliquis, a collaboration between Bristol Myers Squibb (BMS) and Pfizer, total sales amounted to $7.37 billion dollars, reflecting a 9% growthEliquis contributed $13.33 billion to BMS's total sales of $48.3 billion, marking it as a significant revenue driver.

With Keytruda generating nearly $30 billion in sales, Merck managed to remain among the top three companiesMerck’s total revenue reached $64.17 billion in 2024, marking a 7% increase, with Keytruda contributing approximately 46% of that revenue at $29.48 billion.

However, sales from the HPV vaccine Gardasil/Gardasil 9 were disappointing, totaling $8.58 billion, down 3% year-over-year.

In 2024, while Roche, Novartis, and AstraZeneca did not have billion-dollar equivalent blockbuster drugs, their multi-faceted strategy kept their leadership position intact.

Roche's revenue reached approximately 60.49 billion Swiss francs (about $68.89 billion), reflecting a 7% increaseRoche achieved 17 drugs that reached the billion-dollar mark, with the top three drugs together generating over $17 billionA notable player was Vabysmo, a dual-action drug for eye diseases, with its annual revenue increasing by 68%, becoming a backbone of Roche's growth in the year.

Additionally, Eli Lilly, AstraZeneca, Novartis, and Sanofi experienced double-digit growth rates, with AbbVie lagging behind at a growth rate of only 3.7%. Lilly showcased the most explosive growth, with revenues amounting to $45 billion and a growth of 32%. Tirzepatide's sales exceeded $16 billion in a year.

AstraZeneca realized substantial global growth, achieving $54.1 billion in total revenue, increasing by 21%, with oncology and metabolic fields supporting its heavyweight drugs

Farxiga, addressing prevalent chronic conditions, generated $7.717 billion, marking a 31% increase.

Another significant factor was Novartis's revenue, with $50.32 billion recorded, up 12%, supported by 14 “billion-dollar” drugsThe top four drugs alone reached sales of $20 billion, showing growth rates ranging from 25% to 49%. Entresto, a flagship product, raked in $7.822 billion, with a growth of 31%.

Sanofi’s performance in 2024 saw impressive numbers, with revenues of $44.62 billion, bolstered by strong sales of Dupixent, which achieved a record-breaking revenue of €13.072 billion (approximately $14.179 billion).

On the other hand, AbbVie saw its sales of Humira fall to $8.993 billion, a year-over-year decline of 37.6%, which weighed on its overall performanceAbbVie's total revenue for the year was $56.33 billion, with a growth of only 3.7%, positioning it at the bottom of the growth rankings among the top ten companies.

Beyond the top lists, some companies deserve attentionNovo Nordisk, while not entering the top ten rankings, still generated sales of $42.1 billion with a growth rate of 26%, positioning itself as a potential contender for the top ten in 2025.

However, the billion-dollar drug sales cannot be viewed as a long-term solution; the looming patent cliff is a common hurdle all pharmaceutical firms will faceReports from Leerink Partners indicate that from 2025-2030, Bristol Myers Squibb, Merck, Amgen, Novartis, and AstraZeneca will face significant competition from generics and biosimilars, whereas Vertex, Gilead, Sanofi, Novo Nordisk, and Lilly will experience the least pressure during this period.

Pharmaceutical giants are simultaneously tweaking patent strategies to extend drug lifespans while engaging in a buying spree to acquire small, innovative drug companies and pipelines that are drawing merger and acquisition interest

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