The past few years have seen fluctuations in drug sales. While patent expiries remain a major cause of the decline in sales of a particular drug, the Covid-19 pandemic and the rise of weight loss therapies have resulted in high revenue for these therapies.

The Covid-19 vaccine sales caused Pfizer and Moderna’s profits to skyrocket during the pandemic. However, the vaccine sales have dried up in the last year, causing companies like Pfizer to institute cost-saving measures. Merck & Co.’s (MSD) Keytruda (pembrolizumab) has been one of the highest grossing drugs for the past few years. It only secured the number one spot in 2023, falling behind AbbVie’s Humira (adalimumab), which held the title of the world’s bestselling drug for nine years in a row until Pfizer and BioNTech’s Covid-19 vaccine Comirnaty knocked it off the top ranking in 2021.

Patent expiry and the introduction of generics have caused massive revenue decline for previously top-selling drugs such as AbbVie’s Humira and Rinvoq (upadacitinib). Thereby, losing their top 10 spot, with Humira falling to number 12, as its sales were down by 37.6% from the previous year to $8.99 billion. Rinvoq’s sales were down by half (50.4%) to just $5.97 billion in 2024.

BMS’s cancer blockbuster drug, Opdivo (nivolumab) also lost its number nine spot, despite its sales increasing by a modest 3%, falling to number 11.

New entrants to the top 10 list included AbbVie’s successor to Humira, Skyrizi (risankizumab), Eli Lilly’s type 2 diabetes therapy Mounjaro (tirzepatide), and Vertex Pharmaceuticals’ cystic fibrosis therapy Trikafta/Kaftrio (elexacaftor/tezacaftor/ivacaftor and ivacaftor). Skyrizi sales were up 50.9% from 2023 to $11.72 billion, catapulting it from number 14 to number six on the list. Mounjaro secured its number eight spot after its sales increased by a whopping 124% from $5.2 billion in 2023 to $11.5 billion in 2024.

1. Keytruda (pembrolizumab)

Keytruda was finally able to claim the title of the world’s bestselling medicine in 2023, after AbbVie’s Humira lost US market exclusivity and as demand for Covid-19 vaccines plummeted at the end of the pandemic. The programmed cell death 1 (PD-1) inhibitor is the highest-grossing drug in MSD’s portfolio.

In 2024, Keytruda’s sales grew by 18% to $29.5 billion. The drug also saw three US Food and Drug Administration (FDA) approvals last year. In January 2024, the US regulatory agency approved Keytruda in combination with chemoradiotherapy (CRT) for the treatment of patients with FIGO (International Federation of Gynecology and Obstetrics) 2014 Stage III-IVA cervical cancer.

In June 2024, the US FDA approved the combination treatment of Keytruda, carboplatin and paclitaxel, followed by Keytruda as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.

In September, MSD received FDA approval for using Keytruda in combination with pemetrexed and platinum chemotherapy as the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM). MSD also successfully trialed the subcutaneous formulation of the therapy, with a Phase III trial finding it to be non-inferior to the intravenous version.

MSD also suffered some setbacks in expanding Keytruda’s use in oncology. In August 2024, the company discontinued two Phase III trials, KEYNOTE-867 and KEYNOTE-630, evaluating Keytruda’s use in lung and skin cancers respectively. The news came after an independent Data Monitoring Committee (DMC) review found that the trials were unlikely to meet their primary endpoints.

In a September 2024 meeting, the US FDA’s Oncology Drugs Advisory Committee voted to limit the use of Keytruda along with other PD-1 inhibitors such as Bristol Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab). The committee voted 11-1 that the risk-benefit assessment is not favorable for the use of checkpoint inhibitors (CPIs) in patients with metastatic or unresectable esophageal squamous cell carcinoma with PD-L1 expression less than 1.

2. Ozempic (semaglutide)

The sales and popularity of Ozempic, along with its weight loss counterpart Wegovy (semaglutide), has allowed Novo Nordisk to generate DKK290.4 billion ($40.3 billion) in revenue in 2024. The company’s glucagon-like peptide 1 (GLP-1) agonists as part of its diabetes and obesity portfolio accounted for about 93.5% of the total sales last year.

The massive popularity of Ozempic has resulted in massive demand for the product. Throughout 2023 and 2024, Novo Nordisk struggled with supply constraints, with the US FDA putting Ozempic and Wegovy on its shortage list of medications at one point. As a result, 2024 saw massive investment from Novo Nordisk in expanding its manufacturing capabilities. Novo Holdings paid $16.5 billion to acquire the contract development and manufacturing organization (CDMO) giant Catalent, allowing Novo Nordisk to secure three more fill-finish sites from its sister company.

Novo Nordisk has also invested in building up its manufacturing facilities. In June, the Danish pharmaceutical giant unveiled plans to spend $4.1 billion to build a second manufacturing plant in Clayton, North Carolina.

Novo Nordisk Pharmatech, a unit that specializes in producing drug ingredients, noted that it is spending 1.5 billion Danish kroner ($220 million) to build a plant in Køge, Denmark, that will make raw materials. The company also plans to invest about $409 million to set up a quality control hub in Denmark as well.

Novo Nordisk has enjoyed a first-to-market sales advantage with its obesity counterpart Wegovy. However, it is facing stiff competition from Eli Lilly’s dual glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) agonist drug Zepbound (tirzepatide), which pulled in $4.9 billion in sales last year. Lilly’s type 2 diabetes treatment, marketed as Mounjaro (tirzepatide), raked in $11.4 billion in sales last year, catapulting it to being the eighth highest grossing medication in 2024.

3. Dupixent (dupilumab)

The sales for Sanofi and Regeneron Pharmaceuticals’ monoclonal antibody, Dupixent (dupilumab), have been steadily increasing in recent years. The monoclonal antibody is the highest grossing drug in Sanofi’s portfolio, raking in €13 billion ($13.5 billion) in global sales last year.

In September 2024, the US FDA approved Dupixent for chronic obstructive pulmonary disease (COPD), marking its sixth indication and making it the first biologic approved for COPD. Dupixent is also approved for conditions including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis.

The companies have no plans to stop at just six indications and are evaluating the therapy in other immunological indications. In February, Sanofi and Regeneron announced that the US FDA has accepted a supplemental biologics license application (sBLA) of Dupixent as a treatment for rare autoimmune skin disorder bullous pemphigoid (BP). The decision for the priority review is expected by 20 June 2025.

Despite the commercial success, tensions between Regeneron and Sanofi have escalated. In November 2024, Regeneron filed a lawsuit against its longtime partner, alleging that Sanofi “breached certain provisions” and failed to provide adequate commercialization details relating to Dupixent.

Specifically, Regeneron claims Sanofi failed to provide “full access to material information” regarding the contracts with pharmacy benefit manager (PBM) and other payers, including discounts and rebates, which make up the final pricing of the drug. Adding that the refusal implies that Sanofi has “[essentially] replaced its information sharing provision with a “trust Sanofi” provision.”

The lawsuit goes on to claim that Sanofi has blocked Regeneron’s attempts to audit its “books and records related to Dupixent.”

Adding, Regeneron’s partial audit, without access to PBM agreements, has “identified a significant monetary adjustment, many multiples of $75,000, that Defendants owed Regeneron in connection with commercializing Dupixent. Examining the PBM Agreements could uncover even larger errors resulting in adjustments in Regeneron’s favor.”

Sanofi has publicly claimed that ‘[it is] fully compliant with the terms of our collaboration agreement with Regeneron.”

4. Biktravy (bictegravir, emtricitabine and tenofovir alafenamide)

Biktravy remains the top selling product for the treatment of human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS). The drug sales were up by 13% to a total of $13.2 billion, and accounted for 45.8% of Gilead’s overall product sales last year.

Biktravy is a fixed dose combination therapy consisting of an integrase strand transfer inhibitor (bictegravir) and two HIV-1 nucleoside analog reverse transcriptase inhibitors (emtricitabine and tenofovir alafenamide). In April 2024, the US FDA approved to expand the drug’s label to allow its use in pregnant adults with HIV. Another approval, earlier in the year, added patients with suppressed viral loads and M184V/I resistance, a common form of treatment resistance.

Gilead also has another HIV therapy in its portfolio, Descovy (emtricitabine and tenofovir alafenamide), which raked in $2.1 billion in sales in 2024.

Biktravy’s main competitor is GSK and J&J’s cabotegravir, marketed as Apretude and Cabenuva (extended release version). GSK’s HIV portfolio, consisting of Apretude and Cabenuva along with the combination drug Dovato (dolutegravir/lamivudine), generated £7 billion ($8.9 billion) in sales last year.

5. Eliquis (apixaban)

Elquis (apixaban) remained the top selling drug for Bristol Myers Squibb (BMS). It also became one of Pfizer’s top earners as the profits from its Covid-19 products dried up in 2024. The drug generated $13.22 billion in global sales last year, up 9% from the previous year’s sales of $12.9 billion.

Elquis was first approved by the US FDA to reduce the risk of stroke and dangerous blood clots (systemic embolism) in patients with atrial fibrillation that is not caused by a heart valve problem in 2012. Since then, it has been approved for treating deep vein thrombosis (DVT) and pulmonary embolism (PE).

While the drug remains a top selling, its key patents are set to expire around 2031. The companies have been fighting the entry of generic rivals of Elquis in recent years. As early as 2017, BMS and Pfizer have filed multiple patent infringement lawsuits against 25 companies to prevent FDA approval of their generics.

Along with a potential generic competition, Elquis may take a price hit in the US as it is included in the Inflation Reduction Act (IRA) drug price negotiations list. The US Centers for Medicare & Medicaid Services (CMS) announced lower Medicare Part D prices for 10 drugs that will take effect in 2026. The agency notes a 56% reduction in the negotiated price of 30-day supply to $231, compared to the 2023 list price of $521. However, BMS’ CEO Chris Boerner in a quarterly conference call has noted that “now that we’ve seen the final price, we’re increasingly confident in our ability to navigate the impact of IRA on Eliquis.”

6. Skyrizi (risankizumab)

Last year saw the sales of Skyrizi (risankizumab) skyrocket from $7.7 billion in 2023 to $11.7 billion. This is in line with the explosive growth the therapy has shown since its initial approval for moderate to severe plaque psoriasis in 2019.

Skyrizi is an interleukin-23 (IL-23) inhibitor. The therapy is approved for multiple indications including plaque psoriasis, psoriatic arthritis, and Crohn’s disease. Last year, the FDA approved to expand Skyrizi’s label to treat ulcerative colitis.

While current Skyrizi sales are nowhere near the peak sales of AbbVie’s immunology megablockbuster Humira (adalimumab), which recorded peak sales of $21.2 billion in 2022. The drug is well on its way and has overtaken current Humira sales, especially since Humira sales declined by 37.6% in 2024 to $8.99 billion.

AbbVie’s second Humira successor Rinvoq (upadacitinib), a Janus kinase (JAK) inhibitor, also saw a 50.4% jump in sales in 2024 compared to the previous year. The drug raked in $5.97 billion in sales in 2024, making the combined revenue for its immunology medicines, Skyrizi, Rinvoq and Humira, to be $26.68 billion.

Skyrizi’s main competitor is J&J’s Stelara (ustekinumab), which is approved for all the same indications in the US. Stelara generated $10.3 billion in sales in 2024, a slight decline from the previous year’s sales of $10.86 billion.

7. Darzalex (daratumumab)

The Darzalex franchise, including the subcutaneous formulation Darzalex Faspro, was J&J’s largest brand last year, overtaking Stelara, which saw its sales eroded due to the market entry of generics.

The sales for the anti-CD38 monoclonal antibody have been steadily increasing, and the drug has established itself as a market leader as a multiple myeloma therapy. Darzalex has been approved as a combination therapy for different populations of multiple myeloma, including with AbbVie’s Kyprolis (carfilzomib).

In September last year, J&J presented data from a Phase III CEPHEUS study (NCT03652064), which evaluated Darzalex Faspro combined with bortezomib, lenalidomide and dexamethasone (VRd) in first-line, transplant ineligible multiple myeloma patients. The addition of Darzalex Faspro to VRd showed a significant improvement in minimal residual disease (MRD) negativity rates, progression-free survival (PFS) and the rates of complete responses (CR) or better, compared to VRd.

Apart from multiple myeloma, in 2021, the US FDA granted an accelerated approval to Darzalex Faspro as a combination therapy to treat newly diagnosed patients with light chain amyloidosis, a rare disease caused by abnormal buildup of the amyloid protein.

8. Mounjaro (tirzepatide)

Last year was a blockbuster year for metabolic therapies, with two type 2 diabetes therapies making it into the top 10 high grossing drugs list. 2024 also saw a booming global demand for Mounjaro (tirzepatide).

Mounjaro is a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide 1 (GLP-1) agonist. The other tirzepatide product, which is approved as a weight loss treatment and is marketed as Zepbound, also generated $4.9 billion in sales in 2024. The company also expanded Zepbound’s label to treat moderate to severe obstructive sleep apnea in December 2024.

Mounjaro has seen a massive spike in sales since its US approval as a treatment for type 2 diabetes in May 2022. Sales for the type 2 diabetes therapy were up by 124% to $11.5 billion, compared to $5.2 billion in 2023.

The drug’s popularity did come at a cost, as Lilly suffered shortages of Mounjaro and Zepbound since late 2022. The company has invested billions of dollars to expand its manufacturing capabilities. The US FDA only reaffirmed its assessment that both drugs are “no longer in shortage” in December of last year.

The drug shortages also lead to an increase of counterfeit version of GLP-1 medications, Mounjaro, Zepbound, Ozempic and Wegovy, popping up all over the world. Leading to both the FDA and the respective companies, Lilly and Novo Nordisk, to warn against the use of counterfeit versions. The US regulatory agency also sent out numerous warning letters to compounding pharmacies for illegally selling semaglutide and tirzepatide, or producing adulterated or misbranded versions.

9. Trikafta/Kaftrio (elexacaftor/tezacaftor/ivacaftor and ivacaftor)

The sales for Vertex Pharmaceuticals’ Trikafta/Kaftrio (elexacaftor/tezacaftor/ivacaftor and ivacaftor) have been steadily increasing, with it raking in $11.02 billion in 2024, a 12% increase compared to the previous year.

The US FDA initially approved Trikafta in 2019 as a treatment for cystic fibrosis patients aged 12 years and older. The US regulatory agency has since expanded the drug’s label to include cystic fibrosis patients between the ages of two and 11 with certain mutations. In December last year, the US FDA approved Trikafta’s use in use in children as young as two years with at least one F508del mutation or a responsive CFTR mutation.  

The drug previously carried a precaution about elevated liver enzymes, but this has been elevated to a boxed warning for liver-related risks including liver faliure. Patients using Trikafta require regular liver function monitoring according to the US FDA.

Last year also saw Vertex expand its portfolio of marketed therapies to include another cystic fibrosis therapy Alyftek (vanzacaftor/tezacaftor/deutivacaftor), a next-generation cystic fibrosis transmembrane conductance regulator (CFTR) modulator, along with a beta thalaseemia and sickle cell disease CRISPR cell therapy, Casgevy (exagamglogene autotemcel). Earlier this year, the US FDA approved Vertex’s non-opioid pain medication, Journavx (suzetrigine).

10. Stelara (ustekinumab)

While Stelara (ustekinumab) was the top selling drug for J&J in 2023, last year saw its sales slip by 4.6% to $10.3 billion. The company’s multiple myeloma therapy, Darzalex, overtook it as the highest grossing therapy in 2024.

Stelara is a human interleukin-12 and -23 (IL-12 and 23) antagonist, which was first approved by the US FDA to treat psoriasis in 2019. Its approval was later expanded to include Crohn’s disease, active psoriatic arthritis, and ulcerative colitis.

In addition to facing competition from AbbVie’s IL-23 inhibitor, Skyrizi, the drug is expected to see the launch of its biosimilar versions. J&J has already settled three lawsuits with multiple companies, including Amgen, to push the launch of the Stelara biosimilar’s release date to 2025.

The Stelara biosimilars have already launched in the US. Amgen’s Wezlana was the first to debut in the US on 17 January 2025. Alvotech and Teva’s Selardsi launched a month later on 21 February, with Samsung Bioepis and Sandoz’s Pyzchiva and Biocon’s Yesintek following on 24 February. Wezlana was also given interchangeable status by the FDA, allowing pharmacists in some states to switch patients from the reference product to the biosimilar without notifying prescribers.

J&J has made moves to position another of its monoclonal antibodies, Tremfya (guselkumab), as a successor to Stelara. The IL-23 and D64-inhibiting monoclonal antibody was first approved as a treatment for moderate to severe plaque psoriasis by the US FDA, in 2017. The drug has since been approved to treat psoriatic arthritis and most recently ulcerative colitis (in September 2024). J&J reported $3.67 billion in sales for Tremfya in 2024, a 16.6% increase from the previous year.

J&J is also developing a subcutaneous formulation for Temfya. In February 2025, the company reported positive data from a randomized double-blind Phase III Astro trial (NCT05528510), evaluating the subcutaneous version for both induction and maintenance dosing in 418 adults with moderately to severely active ulcerative colitis. Initial 12-week results found patients in the treatment arm seeing a clinical remission rate of 27.6% versus 6.5% for those in the placebo arm.

Note: For the analysis, only the sales of a reported branded product are considered and not the active ingredient. For example, Novo Nordisk’s Ozempic and Wegovy both contain semaglutide, however, the top 10 list in this case did not consider the combined sales of both but rather the reported revenue for Ozempic. Furthermore, the currency conversions for all sales estimates in the series, including 2023 sales, were done in February 2024.