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iStock, leolintang Merck’s Keytruda holds on to the top spot while AbbVie’s Humira—once the world’s top-selling drug—continues to cede its market share to biosimilar competitors. For six years straight, AbbVie’s Humira reigned as the world’s best-selling drug. The anti-TNF antibody bowed only to Pfizer and BioNTech’s COVID-19 vaccine Comirnaty in 2021, and yet even in the throes of the pandemic—when anti-infectives saw a surge in demand—Humira stood its ground, staying in the top three earners of the year. In 2024, however, it became clear that Humira is no longer the dominant market force that it once was. Mounting biosimilar and competitive pressure have sent Humira’s sales steadily downward. The drug is no longer AbbVie’s biggest moneymaker and the pharma appears to no longer be investing in its growth. As per its latest pipeline update document , posted in January, AbbVie has no active studies or applications for Humira. Humira’s fall is emblematic of the typical life cycle of drugs. John Gagliano, senior director at BioPharmCatalyst, expects to see a similar pattern play out in the coming years, as the industry faces the strongest patent headwinds in more than a decade. “The overall landscape [of top drugs] is anticipated to become more diverse as emerging therapies gradually replace aging blockbusters,” he told BioSpace in an email. Companies can implement what Gagliano calls “defensive strategies” such as novel formulations, patent extensions and combination regimens to prolong the exclusivity of their drugs and “sustain their positions” in the market—but that only serves to delay the inevitable. “Many current top sellers face imminent loss of exclusivity (LOE), which will likely trigger rapid revenue declines,” Gagliano continued. In addition to Humira, Eliquis and Opdivo are likely to “drop out of the top ranks as biosimilars and generics enter the market,” predicts Gagliano’s colleague Olivia Tidwell, content coordinator at BioPharmCatalyst. Meanwhile, she continued, potentially rising to take their place are promising assets in emerging modalities, such as radioligand therapies, CAR Ts and gene therapies, among others. Here, BioSpace looks at the top 10 pharma products that brought in the biggest sales in 2024. The list is a mix of predictable and surprising. Novo Nordisk’s Ozempic, for instance, was pretty much a shoo-in for this list, while several drugs facing LOE concerns—and were therefore expected to suffer slower sales—managed to maintain their market dominance. Merck’s Keytruda Tops Again—But for How Long? 2024 Sales: $29.5 billion YOY Change: 18% For the second year in a row, Merck’s blockbuster PD-1 inhibitor Keytruda tops the list of pharma’s best-selling products. In 2024, Keytruda surged 18% year-on-year to hit $29.48 billion in sales . The feat comes as no surprise given how Keytruda has become a cornerstone cancer therapy with more than 40 indications under its belt, including various forms of lung and gynecological cancers. Most recently, the FDA approved Keytruda for the first-line treatment of pleural mesothelioma, giving Merck access to a market that could exceed $12 billion in value by 2034, as per an August 2024 IMARC report . But trouble could be brewing on Keytruda’s horizon. Key patents protecting Merck’s blockbuster are set to expire in 2028, opening it up to biosimilar competition and, in turn, eroding sales. There also appears to be growing regulatory apprehension regarding the widespread use of Keytruda—and PD-1 inhibitors more broadly. In September 2024, an FDA advisory panel overwhelmingly voted to narrow the label of Keytruda, along with Bristol Myers Squibb’s Opdivo and Yervoy, in stomach and esophageal cancers, restricting their use in patients with low PD-1 expression levels. The FDA has yet to put out a formal directive. Merck is doing what it can to maintain Keytruda’s market dominance. The pharma is developing a subcutaneous formulation of the PD-1 blocker that could help maintain an edge over potential copycats. “Unlike Humira’s steep post-LOE slide, Keytruda’s lifecycle management measures suggest it will retain significant market share, albeit potentially at a lower rank,” BioPharmCatalyst analyst Cristian Marulanda told BioSpace in an email. “Merck’s proactive strategies and continuous innovation may help Keytruda weather competitive pressures better than past examples.” IRA Threatens Rise of Novo’s Ozempic 2024 Sales: $16.9 billion YOY Change: 26% It comes as a surprise to no one that the widely popular type 2 diabetes drug Ozempic is among the top-performing drugs of 2024. In its full-year business report, Novo Nordisk revealed that the GLP-1 therapy made more than 120 billion Danish kroner last year, or approximately $16.9 billion. Ozempic was one of the highest-growth assets on this list—relative to 2023, Ozempic’s sales jumped 26%—and it is poised to see an even greater upward trend in coming years. Originally approved in 2017 to improve glycemic control, Ozempic secured additional approvals in 2020 to reduce cardiovascular risk and in January 2025 to lower the likelihood of chronic kidney disease. Getting in the way of Ozempic’s growth, however, is the Inflation Reduction Act (IRA). Earlier this year, the Centers for Medicare and Medicaid Services (CMS) selected the GLP-1 drug—alongside sister brand Rybelsus—for the second round of drug price negotiations. The move was not entirely unexpected . Over the past year, Novo was on the receiving end of several high-profile calls to lower the list price of Ozempic. Faced with the prospects of a price cap on Ozempic, Novo has asked the U.S. Court of Appeals for the Third Circuit to speed up proceedings regarding its ongoing complaint against the IRA. Novo alleges that the price negotiations are in violation of its constitutional rights—an argument that has so far failed to convince judges. Biktarvy Sales Symbolize Gilead’s Strong Standing 2024 Sales: $13.4 billion YOY Change: 13% Building off the size of the HIV market is Gilead’s antiretroviral drug Biktarvy, which in 2024 jumped 13% to bring in $13.42 billion in sales, growth that the pharma attributed to “higher demand” for the drug. Biktarvy is currently the cornerstone of Gilead’s HIV business. It “commands over 50% share of the U.S. market” and is the “regimen of choice” across many markets, commercial chief Johanna Mercier said during the company’s fourth-quarter investor call. Unlike Keytruda and Ozempic, there are no clear headwinds in Biktarvy’s immediate future. Key patent protections for the drug will remain intact in the coming years and will keep generic competitors off the market until 2033. Biktarvy also escaped the CMS’s list for the second cycle of drug negotiations. Still, Biktarvy isn’t a completely risk-free asset for Gilead, and the prospects of price control problems remain on the horizon. In a note to investors in February 2025, analysts at BMO Capital Markets said that they are wary of the drug’s “likely inclusion” in the 2028 cycle of IRA negotiations. BMS, Pfizer Brace for Eliquis LOE 2024 Sales: $13.3 billion YOY Change: 9% The blood thinner Eliquis—developed and commercialized through the powerhouse partnership between Bristol Myers Squibb and Pfizer— made $13.3 billion in 2024, representing a 9% year-on-year increase in sales. The drug has long been a prized asset for both companies, but that may soon be coming to an end. Eliquis is set to lose market exclusivity in 2026—with several generics already lined up, eager to enter the U.S. market and eat into the drug’s earnings. Among these are copycats from Mylan Pharmaceuticals and Micro Labs Limited, which the FDA approved as early December 2019 . Eliquis was also in the first batch of drugs that underwent the CMS drug price negotiations last year. The final maximum fair price of $231 for a 30-day supply, set to take effect in 2026, is a 56% discount from the original cost, though it was already selling below list price . To cope with the potential loss of revenue from Eliquis, BMS has kicked a multibillion-dollar savings initiative into motion, targeting $1.5 billion in cost-cuts by the end of 2025 and another $2 billion through 2027. Pfizer is taking a similar approach, setting a $3.5 billion savings goal in 2024 and tacking on another $1.5 billion by the end of 2027. Sanofi, Regeneron Rely on Robust Dupixent Figures 2024 Sales: $13 billion YOY Change: 23% Sanofi and Regeneron are jointly commercializing the immunology heavy-hitter Dupixent, which last year bagged $13.072 billion , representing 23% year-on-year growth. Like Biktarvy, Dupixent appears to have no patent- and IRA-related issues on its horizon. The drug will retain market exclusivity until 2031 and is looking at promising market prospects, too. The FDA in September 2024 approved Dupixent for the treatment of chronic obstructive pulmonary disease, for which launch is expected this year . Still, analysts at William Blair in a January 2025 report cautioned that Regeneron and Sanofi are “extremely reliant on Dupixent,” with “little else to be excited about” in their pipelines. Regeneron, for instance, has been trying to get its high-dose Eylea brand off the ground with limited success so far. In the fourth quarter, Eylea HD brought in $305 million, below the projected $336 million consensus. Sanofi, meanwhile, is a “bit of a one-trick pony with respect to near-term growth drivers,” according to the William Blair report. Vaccines account for around 15% of its revenue and this space faces considerable exposure due to volatility linked to changes in government policies, the firm wrote. AbbVie’s Skyrocketing Skyrizi 2024 Sales: $11.7 billion YOY Change: 50.9% AbbVie’s answer to Humira’s fall, the anti-IL-23 therapy Skyrizi, is the fastest-growing asset on this list. With a 50.9% year-on-year increase in sales, Skyrizi raked in $11.718 billion for the Illinois pharma in 2024, easily surpassing Humira’s nearly $9 billion earnings. That Skyrizi finds itself on this list is evidence of how well AbbVie handled the lapsed protections for Humira, which for years was the world’s top-selling drug. In the third quarter of 2024, sales of Skyrizi—alongside the JAK inhibitor Rinvoq—helped AbbVie narrowly beat analysts’ expectations , despite continued erosion of Humira’s sales. This trend continued into the fourth quarter. In a Feb. 1 note from BMO Capital Markets, in reaction to the pharma’s full-year business report, analysts said that Skyrizi and Rinvoq are set to “usher in a new era of growth” for AbbVie, which has “finally fully moved on from the narrative of the Humira LOE.” Skyrizi’s immediate future is clear of patent concerns. Market exclusivity is set to last until 2031, as per the January William Blair report. Likewise, Rinvoq’s protections will remain intact into 2033. J&J Offsets Stelara Losses With Darzalex Growth .tg {border:none;border-collapse:collapse;border-spacing:0;} .tg td{border:none;border-collapse:collapse;border-spacing:0;font-family:Arial, sans-serif;font-size:14px;overflow:hidden; padding:10px 5px;word-break:normal;} .tg th{border:none;border-collapse:collapse;border-spacing:0;font-family:Arial, sans-serif;font-size:14px;font-weight:normal; overflow:hidden;padding:10px 5px;word-break:normal;} .tg .tg-ej4a{border:none;border-collapse:collapse;border-spacing:0;font-family:Arial, Helvetica, sans-serif !important;font-size:18px;text-align:left; vertical-align:top} Darzalex 2024 Sales: $11.6 billion YOY Change: 20% Stelara 2024 Sales: $10.4 billion YOY Change: -4.6% J&J had two top-selling drugs in 2024: one on its way in, the other on its way out. Stelara, an anti-IL-12 and IL-23 antibody indicated for various inflammatory diseases, lost key patent protections in September 2023 . Biosimilars have since entered the U.S market and, while not yet completely unseating Stelara, have eroded its sales. In 2023, the biologic made $10.86 billion . Last year, sales were down 4.6% to $10.34 billion. To make up for lost revenue, J&J is leaning on its cancer drug Darzalex, an anti-CD38 cytolytic antibody approved for multiple myeloma. In 2024, Darzalex brought in $11.67 billion, representing nearly 20% year-on-year growth. According to the William Blair report, Darzalex will help drive J&J’s cancer franchise—including its CAR T therapy Carvykti and bispecific antibodies Tecvayli and Talvey—to 15.3% compounded annual growth, hitting $27.1 billion in sales by 2029. J&J continues to work on expanding Darzalex’s label, including a September 2024 FDA filing that would allow the drug’s use in patients with newly diagnosed multiple myeloma who are ineligible for stem cell transplantation, as well as a November 2024 submission for high-risk smoldering multiple myeloma. Darzalex will retain key patent protections until 2029, as per William Blair. Humira: On its Way Out? 2024 Sales: $9 billion YoY Change: -37.6% Sustaining a 37.6% year-on-year decline in sales, Humira is now clearly beyond its prime. In 2024, the once-dominant anti-inflammatory therapy brought in $8.993 billion for AbbVie. The obvious culprit for Humira’s fall from grace is growing biosimilar competition. Since the drug lost key patent protections in 2023, several copycats have hit the market, including Amgen’s Amjevita, Celltrion’s Yuflyma, Cordavis and Sandoz’s Hyrimoz and Boehringer Ingelheim’s Cyltezo. Another major driver of Humira’s market erosion is CVS Caremark’s move in April 2024 to remove the branded drug from its major national formularies in favor of biosimilars, including its own adalimumab brand Hyrimoz. Cordavis is a CVS Caremark subsidiary launched in August 2023. Humira is putting up a commendable fight, though. In the first-quarter 2025 edition of Samsung Bioepis’ Biosimilar Market Dynamics report , Humira remains the top adalimumab brand, controlling 72% of the market. In the third-quarter 2024 edition of the same report, Humira still had 82% market share . Merck’s Gardasil Hangs On Amid Controversy 2024 Sales: $8.6 billion YoY Change: -3% The only vaccine on this list, Merck’s human papillomavirus shot Gardasil saw a 3% drop in sales in 2024, bringing in $8.58 billion . The jab’s prospects don’t look good. Key patent protections are set to expire in 2028, according to William Blair, though there appear to be no notable biosimilars on the horizon. More importantly for Merck and Gardasil are questions surrounding how U.S. health authorities will handle vaccines moving forward with Robert F. Kennedy Jr.—a known vaccine critic—as Secretary of Health and Human Services . In addition, last month, Merck announced that Gardasil shipments to China would be suspended amid stubbornly high inventories of the vaccine, a result that CEO Rob Davis blamed on “increased pressure on discretionary consumer spending” on the pharma’s most recent earnings call. Gardasil was recently approved for males in China.

As Cullinan Therapeutics launches the first U.S. clinical trial of a CD19 bispecific in an autoimmune disease, CEO Nadim Ahmed wants to shape expectations around efficacy.\n Breakthrough research and investor enthusiasm prompted Cullinan Therapeutics to redirect one of its cancer programs toward autoimmune diseases in 2024. Now, CEO Nadim Ahmed wants to reset expectations, hoping that speed and a “thriller or killer” approach will be his friends as the company navigates both competitive fields in parallel.Cullinan’s stock price surged last April after the company unveiled plans to switch the focus of its CD19xCD3 T-cell engager, CLN-978, from blood cancer to lupus and other autoimmune diseases.The pivot was inspired by a 2022 paper describing using anti-CD19 CAR-T therapy in patients with refractory systemic lupus erythematosus (SLE). The results were so impressive that when Ahmed floated the idea of taking CLN-978 into autoimmune diseases with analysts and investors at the 2024 J.P. Morgan Healthcare Conference, he received overwhelmingly positive feedback.Having previously held hematology leadership roles at Celgene and then Bristol Myers Squibb, Ahmed knew how transformative CAR-T therapies can be, but he also understood that the risk-benefit equation is different in autoimmune diseases. “It felt to me that if you have an off-the-shelf regimen that can be potent, with less of the logistics, the manufacturing, potentially better safety profile—because of the risk of secondary cancers—all of those things, that this could really be a very strong idea,” Ahmed recalled.Within a few weeks, Cullinan Oncology became Cullinan Therapeutics, even though a big chunk of the company’s pipeline—including its lead program, which just read out in a phase 2 study for non-small cell lung cancer—remains in oncology. Since then, the company has built an immunology unit, hired in-house rheumatologists to run clinical development on that side, and in October, won FDA clearance to evaluate CLN-978 in humans with moderate to severe SLE. Resetting expectations At this year’s JPM, Ahmed wanted to set the tone for the new Cullinan. The company aims to provide initial SLE data in the fourth quarter “on a meaningful number of patients that can be interpretable,” Ahmed told Fierce on the sidelines of the conference this January.But Cullinan is only one of many that are swept up by this seismic shift in the autoimmune cell therapy world. And investor enthusiasm in Cullinan was not as high as it was a year ago, as the company’s stock price has fallen below its pre-pivot level.Part of the stock fluctuations can be attributed to the macroenvironment, Ahmed said. And another part reflects what he called a disconnect between investor expectations and clinicians’ real-world desire for adoption, a gap that Ahmed is trying to close.To Ahmed, some investors have unfairly upheld CLN-978, an off-the-shelf bispecific, to the same efficacy standard as an autologous CAR-T. Early results from Kyverna Therapeutics’ CAR-T candidate, KYV-101, showed that the one-time therapy could eliminate disease activity, including the need for immunosuppressants and steroids in all patients when given at the desired dose to refractory lupus patients. Although Kyverna investor enthusiasm dropped after a patient receiving a lower dose relapsed, that 100% disease control rate has become a benchmark for all T-cell therapies that want a spot in lupus.  However, after speaking with rheumatologists, Ahmed found the bar is “very different” for an off-the-shelf regimen.“What they tell us is, if today, my patients are not getting into a DORIS remission—at least not with taking them off background therapy as well—if you can get me a minimum of 20% to 30% of my patients, with a safety profile that’s no greater than grade 1 or 2 [cytokine release syndrome], you’re going to get very widespread systematic adoption of this therapy,” Ahmed said.“That doesn’t mean we’re not going to aspire for the highest,” he added. “Of course we are.” An increasingly crowded field If Cullinan investors got excited about a burgeoning opportunity at the beginning of 2024, then they have good reason to be less enthused this year. In the short amount of time, the autoimmune cell therapy field became inundated by players. For CAR-T therapies alone, an article published in October in the journal Bone Marrow Transplantation counted 17 trials globally in autoimmune diseases, including 11 in SLE or lupus nephritis.And that doesn’t even count the many more T-cell engagers like CLN-978 that are itching to have a go at lupus. In October, Benlysta-maker GSK put down $300 million upfront to test Chimagen Biosciences’ CD19/CD20 dual-targeted T-cell engager in lupus and potentially other B-cell-driven autoimmune disorders. New startups such as Candid Therapeutics and Ouro Medicines have recently launched with mega financing rounds with the same goal of developing T-cell engagers for autoimmune diseases.More companies such as Takeda, Nkarta, Sana Biotechnology and IGM Biosciences are also shifting the focus of their oncology CAR or T-cell engager programs to autoimmune diseases.With lupus taking up most of the industry’s interest, Kyverna has instead designated stiff person syndrome, a rare autoimmune neurological disorder, as its CAR-T’s lead indication. But Ahmed argued that the reasons for picking SLE as CLN-978’s initial indication still hold true.“There was a benchmark that, in a way, we kind of had to go to,” Ahmed said, referencing Kyverna’s initial clinical lupus data. Ahmed argued that CAR-T therapies, because of their complicated manufacturing and delivery processes, will likely be limited to a “more narrowly defined patient population” in lupus, whereas bispecifics “could be a solution for the large masses of patients.”Within the T-cell engager class, Ahmed suggested that CLN-978’s high binding affinity for CD19 might differentiate it from competitors.“As you start getting into the short-lived plasma cells, you start to see dimming a little bit of the CD19 expression,” the Cullinan CEO explained. “So, having very high affinity is going to be really important to kind of continue to give that breadth of coverage across the B cell compartment.”Because CLN-978’s binding affinity for CD3 on T cells is in a different range from that for CD19 on disease-causing B cells, it may afford Cullinan a wide window to optimize efficacy while limiting potential immune side effects, Ahmed continued. In addition, CLN-978’s relatively small weight compared with other IgG-based molecules might facilitate better tissue penetration for B cell depletion, he added.These mechanistic theories still need clinical validation, Ahmed acknowledged. The autoimmune cell therapy field remains very young and requires a deeper understanding of the biology. Researchers and drug developers still don’t have clear answers to many key questions, such as the depth of B cell depletion needed to achieve a remission, the duration of response and the possibility of retreatment.Last year, a study published in The New England Journal of Medicine described a case of aggressive refractory SLE that achieved a drug-free complete remission after receiving Johnson & Johnson’s BCMAxCD3 bispecific Tecvayli. The findings add to the unknowns because the B cell subtypes covered by anti-BCMA and anti-CD19 therapies are different.  Ahmed noted that BCMA bispecifics have shown a higher risk of infection in its currently FDA-approved multiple myeloma indication, so “you have to go into it eyes wide open.”The Cullinan helmsman didn’t directly answer whether the biotech will work on a BCMA candidate to complement CLN-978, but said “we’re thinking about continued opportunities in the autoimmune disease space.”CLN-978 has one more advantage—it\'s the first and so far the only CD19 T-cell engager cleared to enter a lupus clinical trial in the U.S. Cullinan is also plotting a rheumatoid arthritis study for the asset in the second quarter. ‘Let’s generate data as quickly as possible’ Meanwhile, Cullinan\'s four other clinical programs are all in oncology. The biotech and its partner Taiho are preparing to pursue accelerated approval in lung cancer for their EGFR exon20 inhibitor zipalertinib later this year after the program met its primary endpoint of overall response rate in a pivotal phase 2b in January. If the drug is approved, Cullinan is on tap for 50-50 profit sharing and has a co-commercialization option which Ahmed said could be cost-efficient if the company’s pipeline continues to advance.The company also has an anti-MICA/B antibody, called CLN-619, that’s in phase 1 testing in both multiple myeloma and solid tumors.Hematology, solid tumors and autoimmune disease, plus a “modality-agonist” approach—that looks like quite a lot for a biotech that’s less than 10 years old. “At the beginning, you have to start off with multiple molecules, because you don’t know which one’s going to make it,” Ahmed said.“The way we approach this is, let’s generate data as quickly as possible,” he continued. “If we generate clinical data as quickly as possible, that’s going to drive value, and that gives us optionality.”Ahmed is pairing fast data generation with a “thriller or killer experimentation approach.” That means maintaining a very high bar for moving assets forward and nixing program quickly if it fails to meet the bar. Cullinan recently returned a B7H4x4-1BB bispecific candidate to Harbour BioMed after seeing phase 1 data. The termination was due to the lack of clear single-agent activity of the molecule rather than freeing up resources for CLN-978, Ahmed explained.As to whether the firm will raise the bar further to give CLN-978 more oxygen, Ahmed pointed to the $280 million oversubscribed private placement it announced alongside the autoimmune pivot in 2024, noting that the $640 million in cash the company had as of the end of September was enough to support operations into 2028.“Now, can you do 20 randomized phase 3 studies? That’s very different,” Ahmed said. “But I don’t have to worry about that right now. We got to generate the data that’s going to drive value first.”