How do small-molecule drugs rank in the strategy of the bio/pharmaceutical majors? What are the leading products from a revenue perspective, and what are key developments on a commercial and pipeline basis? DCAT Value Chain Insights looks at what may in store for 2025.

Small molecules and blockbusters
One way to evaluate how small-molecule drugs are positioned in the product portfolios of the large bio/pharmaceutical companies is to look at the number of blockbusters (defined as products with revenues of $1 billion or more) that are small-molecule drugs. While biologics hold an increasingly larger share of the industry’s and individual companies’ top-selling products, small-molecule drugs still hold an important revenue position among certain companies. With 2024 full-year revenues slated to be reported later this month and next month (January and February 2025), we analyzed sales from 2023 to examine the top-selling small-molecule drugs among some of the pharma majors.

Of the 14 companies analyzed based on 2023 sales, companies leading with small-molecule blockbuster drugs included: Pfizer, Novartis, AstraZeneca, Johnson & Johnson, AbbVie, GSK, Bristol-Myers Squibb, Gilead Sciences, and on the strength of their Type 2 diabetes and obesity drugs, Novo Nordisk and Eli Lilly. Sanofi, Amgen, and Merck & Co., had more limited play in small-molecule blockbuster drugs, and Roche’s top-selling drugs were wholly biologics. A roundup of some of the top-selling small-molecule drugs are highlighted below.

Pfizer’s top-selling small-molecule drug is Eliquis (apixaban), an anticoagulant, with alliance revenues (co-commercialized with Bristol-Myers Squibb) and direct sales of $6.75 billion in 2023, followed by its breast cancer drug, Ibrance (palbociclib), with 2023 revenues of $4.75 billion, and the Vyndaqel (tafamidis) family of products for treating cardiomyopathy caused by transthyretin mediated amyloidosis, a rare disease, with 2023 revenues of $3.32 billion. In all, Pfizer had seven small-molecule blockbuster drugs in 2023. The others were: Xeljanz (tofacitinib), used to treat a number of inflammatory conditions, including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis, with 2023 sales of $1.7 billion; Xtandi (enzalutamide) for treating prostate cancer, $1.2 billion; Paxlovid (nirmatrelvir/ritonavir) for treating COVD-19, $1.3 billion; and Inlyta (axitinib) for treating advanced kidney cancer, $1.0 billion.

As did Pfizer, Bristol-Myers Squibb (BMS) also scored with Eliquis (apixaban), an anticoagulant, posting 2023 revenues of $12.2 billion. It next leading small-molecule drug was Revlimid (lenalidomide) for treating multiple myeloma and other blood disorders with 2023 sales of $6.1 billion although the drug faces generic-drug incursion. Other small-molecule blockbusters drugs from BMS included: Pomalyst/Imnovid (pomalidomide) for treating multiple myeloma and AIDS-related Kaposi sarcoma, with 2023 sales of $3.4 billion; Sprycel (dasatinib) to treat certain types of leukemia with 2023 sales of $1.9 billion; and Abraxane with sales of $1.0 billion although that drug also faces generic-drug incursion.

Novartis’ leading small-molecule drug was Entresto (sacubitril/valsartan) for treating heart failure with 2023 sales of $6.0 billion, with six other small-molecule drugs with sales between $1.3 billion to $2.3 billion in 2023. These were; Promacta/Revolade (eltrombopag) to treat thrombocytopenia (abnormally low platelet counts) and severe aplastic anemia; Kisqali (ribociclib) for treating certain forms of breast cancer; Tafinlar (dabrafenib) + Mekinist (trametinib) for treating certain cancers; Tasigna (nilotinib) for treating chronic myeloid leukemia; Jakafi (ruxolitinib) for treating certain blood cancers; and Sandostatin (octreotide) for treating acromegaly and severe diarrhea/flushing episodes associated with certain tumors.

AstraZeneca had two small-molecule drugs nearing $6.0 billion in sales in 2023: Farxiga (dapagliflozin) for treating Type 2 diabetes, with sales of $5.96 billion and Tagrisso (osimertinib) for treating non-small cell lung cancer, with 2023 sales of $5.80 billion. Other top-selling small-molecule drugs were Lynparza (olaparib) for treating advanced ovarian and prostate cancer, $2.8 billion; Calquence (acalabrutinib) for treating certain blood cancers, $2.5 billion; Symbicort (budesonide and formoterol) for treating asthma and chronic obstructive pulmonary disease, $2.4 billion; Brilinta (ticagrelor) for treating acute ischemic stroke, coronary artery disease and acute coronary syndrome, $1.3 billion; and Crestor (rosuvastatin) for treating high cholesterol, $1.1 billion.  

AbbVie’s leading small-molecule drug is Rinvoq (upadacitinib) with 2023 sales of nearly $4.0 billion, for treating a number of inflammatory conditions, including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis; it is positioned as a follow-up to AbbVie’s top-selling drug, Humira (dalimumab). Other top-selling small-molecule drugs for AbbVie (based on 2023 sales) include: Imbruvica (ibrutinib) for treating certain blood cancers, with sales of $3.6 billion; Vraylar (cariprazine) for treating major depressive disorder and for treating manic, mixed episodes, or depressive disorders associated with Bipolar I disorder, with sales of nearly $2.8 billion; Venclexta (venetoclax), for treating chronic lymphocytic leukemia, small lymphocytic lymphoma, or acute myeloid leukemia, $2.3 billion; Mavyret (glecaprevir/pibrentasvir for treating chronic hepatitis C, $1.4 billion; and Linzess/Constella (linaclotide) for treating irritable bowel syndrome, $1.1 billion.  

Johnson & Johnson (J&J), which is partnered with AbbVie on Imbruvica, posted 2023 sales for the drug of $3.3 billion, making it the second-highest revenue small-molecule drug for the company behind Invega Sustenna/Xeplion/Invega Trinza/Trevicta (paliperidone) for treating schizophrenia with 2023 sales of $4.1 billlion. Other top-selling small-molecule drugs are: Erleada (apalutamide) for treating prostate cancer, $2.4 billion; Xarelto (rivaroxaban), an anticoagulant, with 2023 sales of $2.4 billion; Opsumit (macitentan) for treating pulmonary arterial hypertension (PAH), with 2023 sales of nearly $2.0 billion, and Uptravi (selexipag), also for treating PHA, $1.6 billion; and two HIV drugs, Prezista/ Prezcobix/ Rezolsta/ Symtuza (darunavir), with 2023 sales of nearly $1.9 billion and Edurant (rilpivirine), $1.15 billion.

Both Gilead Sciences and GSK also have several small-molecule blockbuster drugs for treating HIV. Four of five of Gilead’s top-selling small-molecule drugs are for treating HIV, including its top-selling drug overall, Biktarvy (bictegravir, emtricitabine & tenofovir alafenamide), which posted 2023 sales of $11.8 billion. Other small-molecule blockbuster HIV drugs by Gilead are: Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir), with 2023 sales of $2.06 billion; Descovy (emtricitabine & tenofovir alafenamide) with 2023 sales of nearly $2.0 billion; and Odefsey (emtricitabine, rilpivirine, and tenofovir alafenamide), $1.35 billion.

GSK’s top-selling small-molecule drugs are for treating HIV and respiratory diseases. Its HIV drugs include: its dolutegravir products, with 2023 sales of £5.41 billion ($6.59 billion); Dovato (dolutegravir/lamivudine), with 2023 sales of £1.82 billion ($2.22 billion); Triumeq (abacavir/dolutegravir/lamivudine), with 2023 sales of £1.54 billion ($1.88 billion); and Tivicay (dolutegravir),  £1.39 billion ($1.69 billion). Respiratory small-molecule blockbuster drugs (based on 2023 sales) include: Trelegy Ellipta (fluticasone, umeclidinium, and vilanterol), £2.20 billion ($2.71 billion); Seretide/Advair (salmeterol/fluticasone), £1.14 billion ($1.39 billion); and  Relvar/Breo Ellipta (fluticasone furoate/vilanterol, £1.10 billion ($1.33 billion).

For Merck & Co., its key small-molecule blockbuster drug is Januvia/Janumet XR (sitagliptin) for treating Type 2 diabetes with 2023 sales of $3.37 billion, but the drug faces potential downward pricing pressures. While the key US patent for Januvia and Janumet claiming the sitagliptin compound expired in January 2023, as a result of favorable court rulings and settlement agreements related to a later expiring patent directed to the specific sitagliptin salt form of the drug, the company expects that Januvia and Janumet will not lose market exclusivity in the US until May 2026 and Janumet XR will not lose market exclusivity in the US until July 2026; further pediatric exclusivity would extend that until May 2027. Also, the drug is part of the first 10 drugs subject to the Medicare Drug Price Negotiation Program, enacted under the Inflation Reduction of Act of 2022. If the program proceeds as planned, the negotiated prices for these first 10 drugs go into effect on January 1, 2026; however, it has yet to be seen whether the new Administration and Congress in the US will keep this program or roll itback with a change in policy.

Other top-selling small-molecule drugs by Merck & Co include Bridion (sugammadex) for treating neuromuscular blockade under certain conditions for patients undergoing surgery, with 2023 sales of $1.84 billion, and Lynparza (olaparib), for treating certain cancers and for which Merck is partnered for the drug with AstraZeneca, which garnered alliance revenue for Merck of $1.2 billion in 2023.

Momentum into 2025
Glucagon-like peptide 1 (GLP-1) agonists, used to treat Type 2 diabetes and obesity, were the product story of 2024, with both Eli Lilly and Company and Novo Nordisk riding the blockbuster wave for these small-molecule drugs, and momentum is going to continue in 2025 and beyond. Lilly’s Mounjaro (tirzepatide), for treating Type 2 diabetes, registered revenues of $8.0 billion for the first nine months of 2024. Mounjaro was approved in the US for treating Type 2 diabetes in 2022, and in November 2023, the same active ingredient, tirzepatide, was approved in the US for chronic weight management under the brand name, Zepbound, which posted revenues of $3.0 billion in the first nine months of 2024. In late December (December 2024), Zepbound was also approved for treating  adults with moderate-to-severe obstructive sleep apnea and obesity and only prescription medicine for adults with moderate-to-severe obstructive sleep apnea and obesity. Zepbound is a dual-activating GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 obesity medication.

Novo Nordisk has several GLP-1-based products for treating Type 2 diabetes—Ozempic (semaglutide, injection), Rybelsus (semaglutide, tablets), and Victoza (liraglutide)— and two obesity-care GLP-1 products, Wegovy (semaglutide) and Saxenda (liraglutide). Through the first nine months of 2024, revenues for its top GLP-1 agonist diabetes drug, Ozempic, was DKK 86.5 billion ($12.3 billion) and DKK 38.3 billion ($5.4 billion) for its top GLP-1 agonist obesity drug, Wegovy.