Merck’s Keytruda will soon lose exclusivity, just as weight-loss giants Eli Lilly and Novo Nordisk press in with their blockbuster GLP-1s.
King Keytruda, Merck’s blockbuster PD-1 inhibitor, has kept its throne as pharma’s best-selling drug for one more year.
The cornerstone immuno-oncology therapy—which has amassed more than 40 indications—brought in nearly $32 billion in 2025. That was enough to fend off a class of competitors that are quickly gaining ground: GLP-1s. This ascendant drug class has exploded in popularity in recent years, driven largely by its ability to help patients lose weight.
Indeed, with their stratospheric growth, these obesity drugs have set a new standard for mega-blockbuster products.
While Keytruda technically held the top sales spot, Eli Lilly’s tirzepatide brands Mounjaro and Zepbound together made $36.51 billion, eclipsing the cancer powerhouse not even four years into the market.
The same is true for Novo Nordisk’s semaglutide franchise, which includes Ozempic and Wegovy, as well as the older-generation injection Rybelsus. These three products last year brought in $36.19 billion, likewise outpacing Keytruda.
Unlike Keytruda, which is facing near-term loss-of-exclusivity threats, GLP-1s have much more growth ahead of them. In a January 2026 report, analytics firm IQVIA said 2025 was the “year of consolidation” for the obesity space, with clinical evidence, policy, supply chain and market readiness coming together to set the stage for future growth.
2026, IQVIA continued, will be the “year of acceleration” for these drugs, especially as Lilly and Novo—the undisputed market leaders—usher in an era of weight-loss pills, which the firm suggested will mark a “major inflection point in obesity medication accessibility and patient preference.”
Here, BioSpace dives into pharma’s five best-selling products in 2025, looking at the ascent of GLP-1s and the sustaining power of Keytruda, but also at heavy-hitters in the immunology space—relatively understated in terms of headlines, but definitely not in terms of revenue.
Merck’s Keytruda Continues Reign as GLP-1s Close In
2025 sales: $31.7 billion
YoY change: 7%
For the third year, Merck’s cancer blockbuster Keytruda has beaten out all other pharmaceutical products on the market. Last year, the PD-1 inhibitor brought in $31.68 billion across its more than 40 indications, representing a 7% year-on-year increase.
Keytruda faces some stiff competition from Eli Lilly’s tirzepatide franchise. In the third quarter, Keytruda’s earnings were $8.1 billion, while Lilly’s products together made $11.4 billion.
Keytruda is approaching a key turning point in its lifecycle, however, with several crucial patents set to expire in 2028, opening it up to biosimilar competition. Several drugmakers are already moving their copycat formulations through clinical development, according to a 2022 tally by the Generics and Biosimilars Initiative.
Merck is attempting to head off the threat of earnings erosion by producing an under-the-skin version of Keytruda. The FDA signed off on this subcutaneous injection, which now carries the brand name Keytruda Qlex, in September 2025. Last year, Keytruda Qlex hit $40 million in sales.
Keytruda is expected to continue growing as it approaches loss-of-exclusivity, hitting peak sales of $35 billion in 2028, Merck executives said during the pharma’s full-year 2025 earnings call on Feb. 3. Even past the 2028 patent inflection point, as biosimilars enter the market, Merck sees Keytruda Qlex as helping to buttress the product family.
“We continue to think we are going to see 30% to 40% adopted as you get out to 2028,” CEO Robert Davis told investors on the call. “We will drive that as high as we can.”
Lilly’s Mounjaro Edges Out Rival
2025 sales: $22.965 billion
YoY change: 99%
Despite being five years late to the GLP-1 game, Eli Lilly has emerged as the undisputed market champion. The pharma’s type 2 diabetes injection Mounjaro surged 99% year-on-year to earn $22.965 billion in 2025 and become the industry’s second-best-selling drug—while also cleanly surpassing its chief competitor.
Many analysts consider Lilly to have outmaneuvered Novo in the obesity market, coming from behind the Danish giant with a stronger market execution for its products. Indeed, since entering the market in 2022, Mounjaro quickly overtook Novo’s Ozempic with a sales ramp-up that outpaced even Keytruda.
Aside from superior marketing, Lilly’s product also appears to have an efficacy edge over Novo’s, with many studies over the years showing better weight-loss and sugar control figures with tirzepatide.
Now faced with the task of ensuring it stays in the lead, Lilly is looking to expand its obesity business into the oral domain, with orforglipron awaiting a regulatory decision in April. In this market, too, the Indiana pharma is playing catch-up to Novo, which launched its oral form of Wegovy earlier this year.
But Lilly doesn’t seem to be threatened. During the company’s full-year 2025 earnings call, Ken Custer, executive VP of Lilly cardiometabolic health, expressed optimism regarding the success of oral Wegovy, suggesting that it “validates our belief that there’s a substantial number of people with overweight and obesity who’ve been sitting on the sidelines waiting for an oral option.”
Lilly’s other tirzepatide brand Zepbound, which is indicated specifically for chronic weight management, made $13.542 billion in 2025—a 175% increase from the year prior. Taken together, the pharma’s tirzepatide franchise hit $36.507 billion last year, beating out Keytruda.
Taking orforglipron into account, analysts expect Lilly’s obesity trifecta to top $100 billion in peak revenue.
Despite First-Mover Advantage, Novo’s Ozempic Falls Behind
2025 sales: $20.1 billion
YoY change: 10%
After being 2024’s runner-up, Novo Nordisk’s Ozempic fell one spot in 2025 to land behind its chief competitor Mounjaro. The blockbuster diabetes drug, which opened the current era of GLP-1 dominance, brought in $20.1 billion in 2025, a 10% increase over the previous year.
Along with its sister brands Rybelsus and Wegovy, which are specifically indicated for weight-loss, Novo’s semaglutide franchise made roughly $36.19 billion last year, still trailing Lilly’s tirzepatide family.
Novo has largely attributed its market troubles to the rise and persistence of compounders—independent manufacturers that make their own remixed versions of semaglutide. In the early days of the GLP-1 boom, the pharma was unable to keep up with the spike in demand, leaving room for compounders to enter the picture and establish a foothold in the market.
The compounding problem grew big enough that Dave Moore, Novo’s EVP of U.S. operations, conceded in February 2025 that compounders? were “having an impact and it is growing faster than we had anticipated.”
Aside from compounding, CEO Maziar Mike Doustdar also said on the company’s full-year 2025 earnings call last month that declining drug prices in the U.S. were a key commercialization challenge. The Danish giant is among several big pharma companies that have signed pricing deals with the government, offering its GLP-1 products at a discount through the state-sponsored direct-to-consumer platform TrumpRx.
Despite falling behind Lilly, Novo has now been presented with a good opportunity to get back in the market with the FDA’s approval of oral Wegovy. The pill got off to a great start, reaching more than 3,000 patients in just its first week on the market.
Novo has vowed to go “all in” on oral Wegovy, Doustdar said on the earnings call. But given that the pharma has already flubbed a big market advantage once, analysts remain skeptical.
Sanofi/Regeneron’s Dupixent Extends Reign as Most Valuable Immuno Drug
2025 sales: $17.806 billion
YoY change: 26%
Leading the immunology space is Sanofi and Regeneron’s Dupixent, which last year totaled $17.8 billion in sales, representing 26% year-on-year growth.
Unlike Keytruda, Dupixent has no patent problems on its immediate horizon, with key U.S. protections holding until 2031. The drug, which works by disrupting IL-4 and IL-13 signaling to suppress inflammation, has also recently expanded into new indications. In April 2025, Dupixent became the first new FDA-approved therapy in over a decade for chronic spontaneous urticaria. A few months later, the drug became the first targeted therapy for bullous pemphigoid.
Sanofi and Regeneron are continuing to push Dupixent into new therapeutic areas, with a regulatory verdict in allergic fungal rhinosinusitis due by Feb. 28. In April, the FDA is also set to release its decision on the use of Dupixent for chronic spontaneous urticaria in patients aged 2 to 11, according to a corporate presentation last month.
Dupixent is also currently in late-stage development for lichen simplex chronicus and chronic pruritus of unknown origin. Regeneron is also testing a combo regimen of Dupixent with its bispecific antibody Lynozyfic for severe food allergy.
Aside from unlocking new indications, the companies are also improving Dupixent’s formulation , with the goal of prolonging dosing intervals or improving efficacy, RegeneronCSO George Yancopoulos said during the pharma’s full-year 2025 earnings call in January.
Given the drug’s continued development, analysts expect Dupixent to keep gaining through the end of the decade, with BMO Capital Markets estimating in a Jan. 29 note that sales could hit $22.7 billion by 2030.
AbbVie Gracefully Rides Out Humira Cliff as Skyrizi Rises
2025 sales: $17.562 billion
YoY change: 49.7%
Capping off this list is AbbVie, which, in a way, has become a prime example of how to properly manage a patent cliff that would have otherwise been disastrous to a company’s bottom line. In 2025, the IL-23 blocker Skyrizi skyrocketed 49.7% on an operational basis, bringing in $17.562 billion.
AbbVie owns Humira, which was once the world’s most valuable pharma franchise and reigned as the industry’s top-selling product for six years straight. In 2024, however, the anti-TNF therapy started buckling to competitive pressures from biosimilars, which were able to enter the market after Humira’s patent protections expired.
Skyrizi was a fundamental element of AbbVie’s strategy to replace the mega-blockbuster, winning its first FDA approval in April 2019 for moderate to severe plaque psoriasis. The drug has since expanded into inflammatory bowel diseases (IBD), with a Crohn’s disease nod in June 2022 and one for ulcerative colitis in June 2024.
While Skyrizi has so far shown strong growth, investors have raised concerns about its near-term outlook, particularly as the IBD space grows more crowded, according to a Feb. 2 note to investors from William Blair. In March last year, Johnson & Johnson’s IL-23 inhibitor Tremfya won the FDA’s nod for Crohn’s disease, then months later earned another for ulcerative colitis.
The analysts nevertheless expect Skyrizi to “continue to command dominant share in key markets.”
Also crucial to AbbVie’s survival of the Humira cliff is the JAK inhibitor Rinvoq. The drug made $8.3 billion last year, a 38.8% year-on-year increase, finishing as 2025’s ninth best-selling medicine.
