Houlang Forest Research Laboratory|The preface is edited and coordinated|Xu Jiawei's big medicine king must start with $10 billion. This is the latest definition of the global drug king. Five of the world's 12 pharmaceutical companies have revenues of more than $50 billion, and Johnson & Johnson has 851$5.9 billion tops the list, followed by Roche, Merck, Pfizer and AbbVie; There are 3 companies with profits of more than 10 billion US dollars, in order Roche, Johnson & Johnson, Novo and Nordisk. The most profitable is Novo Nordisk, which starts with 336$6.1 billion in revenue generated 12.1 billion$2.8 billion in profits, with a growth rate of %. These 12 companies each have their own big products, which we collectively refer to as "Big Medicine King Company". Its name is the Great Medicine KingClosely related to the performance of major pharmaceutical companies is the changes in their respective ace products in 2023, Houlang Forest has sorted out the top 10 list of global best-selling drugs in 2023, among which the new and old drug kings have been replaced, and the latter has emerged, fully demonstrating the competitive vitality and innovation potential of the pharmaceutical industry. 
In 2023, the sales of the top 10 products will all exceed the $10 billion threshold, and the sales of the top three products, Merck's "K drug", psilofi's "dupilumab" and Novo Nordisk's "semaglutide", will all exceed $20 billion. The sales of 7 drugs in the TOP10 maintained growth, and the sales of 3 drugs declined. Merck's ace product "Keytruda", which is called "K drug", replaced AbbVie's "Humira" as the global new drug king with sales of 25 billion US dollars, and Novo Nordisk won 78The high growth rate of 5% ranked third, while the old drug king "adalimumab (Humira)" and Pfizer's new crown vaccine "comirnaty" fell by % respectively, ranking fifth and eighth. The top 10 drugs include 5 monoclonal antibodies, 3 small molecules, 1 peptide and 1 vaccine. From the perspective of indications, there are 3 autoimmune fields, 2 tumor fields, 2 cardiometabolic fields, 2 anti-infection fields, and 1 hematological system. 
The King of New MedicineMerck & Co., Ltd.: PembrolizumabMerck's Keytruda (pembrolizumab) revenue in 2023 is 250$1.1 billion, up 195%。K drug accounted for 535 percent of Merck's total revenue46% of $8.3 billion, a veritable pillar. Drug K is an anti-PD-1 monoclonal antibody, which was first approved by the US FDA in September 2014, and is the second PD-1 monoclonal antibody approved in the world, which has been approved for 45 indications in 18 tumors. In 2018, K ranked 5th among the world's best-selling drugs with sales of $7.2 billion; In 2023, Humira will officially replace AbbVie as the new overlord of the global medicine king. 
The future development strategy of K drug is combination chemotherapy, combination targeting**, and combination ADC, and Merck has introduced a number of potential ADC pipelines from Columbus and Daiichi Sankyo, and it is expected that the peak sales of K drug will reach $30 billion in the future. Note that the patent for drug K expires in 2028. In addition, Merck's blockbuster products have also seen significant growth in HPV vaccines (quadrivalent and nine-valent), with total sales of 88 in 2023$8.6 billion, a year-on-year increase of 288%。The growth is mainly attributable to the strong demand in China, which is expected to increase further after Merck and Chinese vaccine leader Zhifei reached a sales agreement for this vaccine in 2023. New challengersNovo Nordisk: SemaglutideSemaglutide is a GLP-1 peptide drug developed by Novo Nordisk, including 3 brands: semaglutide hypoglycemic injection ozempic, hypoglycemic tablet Rybelsus, and ** injection Wegovy. Novo Nordisk's revenue in 2023 will be $33.7 billion, a year-on-year increase of 31%; The three brands of semaglutide contributed a total of 211$1.3 billion, an increase of 875%。Among them, ozempic138US$5.9 billion, a year-on-year increase of 60%; rybelsus27.US$1.5 billion, a year-on-year increase of 66%; wegovy45.US$3.8 billion, a year-on-year increase of 407%. On January 26, 2024, Novo Nordisk's semaglutide tablets (Novo Xin) were approved by the State Food and Drug Administration for the treatment of **type 2 diabetes. It is also the first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for marketing in China. Semaglutide has made breakthroughs not only in diabetes and obesity indications, but also in the fields of heart failure and kidney disease. In August 2023, the Phase III STEP HFPIF trial of the product** for heart failure achieved positive results. In October of the same year, the phase III flow study of semaglutide** in patients with type 2 diabetes mellitus and chronic kidney disease was terminated early due to excellent efficacy. In order to solve the problem of semaglutide production capacity, Novo Nordisk will invest a total of more than DKK 75 billion in 2023 alone to expand its production sites around the world. Evaluate analysts**, semaglutide sales will exceed $28 billion in 2024, and it is expected to surpass Keytruda to become the new "drug king". At present, Novo Nordisk has a market of more than 500 billion US dollars, making it the European company with the highest market capitalization. Semaglutide's biggest competitor is Eli Lilly's GIPR GLP-1R dual agonist tirzepatide (tirpatide), which was first approved for marketing in the United States in May 2022 for *** type 2 diabetes, trade name: mounjaro, approved in November this year for ** indication, trade name Zepbound. In 2023, the sales of tirpatide will be 53400 million US dollars, the volume rate shocked the market, becoming the fastest ramp-up drug in history, and is regarded as a strong contender for the future drug king. 
Sanofi and Regeneron: DupilumabDupilumab is an anti-IL-3 IL-4 monoclonal antibody jointly developed by Sanofi and Regeneron, which is mainly used for atopic dermatitis and other chronic immune system diseases. In 2023, Sanofi's dupilumab sales were 1071.5 billion euros (approx. 11.5 billionUS$700 million), a year-on-year increase of 34%. Regeneron's dupilumab achieved 115 in 2023Sales of $8.8 billion increased by 34%, of which the U.S. contributed 88$5.6 billion in sales. 
In June 2020, dupilumab was approved for marketing for the first time in China, and up to now, moderate to severe atopic dermatitis (the population has been expanded to 6 months to **) has been approved in China for the indications of prurigo nodosum and asthma. In January 2024, dupilumab was approved in the U.S. for a new indication in chronic obstructive pulmonary disease (COPD)**, the first and only treatment for patients aged 1 to 11 years with eosinophilic esophagitis (EOE). Regeneron expects to report results from a Phase 3 study in patients with chronic spontaneous urticaria (CSU) who have failed to respond to the biologics of dupilumab** in the fourth quarter of 2024. Note that the dupilumab patent expires in 2028. 
BMS vs. Pfizer: apixabanEliquis (apixaban) is a novel oral anticoagulant drug that prevents thrombin production and thrombosis by reversible, highly selective inhibition of factor XA. Eliquis is jointly developed by BMS and Pfizer and is the best-selling small molecule chemical drug. Since its launch in Denmark in 2011, Eliquis has been a reliable growth driver for Bristol-Myers Squibb (BMS) and Pfizer, with sales of $189 in 2023$8.3 billion, compared to $18.2 billion in 2022$6.9 billion, up 39%。Of these, Pfizer sold 67US$4.7 billion, up 5% year-on-year; BMS sales were $12.2 billion, up 4% year-on-year. Apixaban is about to face a patent cliff. In August 2017, the USPTO granted Eliquis a patent for a key composition, extending its term of protection until November 2026. In addition, another of Eliquis' formulation patents expires in 2031. During the patent protection period, it will take time for generic drugs to be marketed, and the exclusive right of Eliquis in the market is an important factor to ensure the stable growth of its performance. The Great Medicine King has changedAbbVie: adalimumabAccording to the financial report, AbbVie's revenue in 2023 will be 5431.8 billion US dollars, down 64%。The former "king of medicine" adalimumab (Humira) has an annual income of 1440.4 billion US dollars, a year-on-year decrease of 322%。Humira was launched in the United States as early as 2002 and has long dominated the sales charts for many years, and has now been approved for 17 indications worldwide, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, etc. Since its listing, Humira has won nearly 2$2 trillion in total sales. With the advent of patent cliffs and biosimilars, Humira has stepped down from the altar. In the United States, the market exclusivity period for adalimumab ended in January 2023; Amjevita, an adalimumab biosimilar developed by Amgen, entered the U.S. market, and biosimilars have begun to eat into adalimumab sales. In addition, adalimumab biosimilars from Boehringer Ingelheim, Novartis Sandoz, Organon, Pfizer, Viatris, Cohereus and Fresenius Kabi will also be available in the United States. On January 3, 2024, the US PBM giant CVS announced that it would remove Humira from the priority list of some drugs on April 1, while Humira's biosimilars will remain in the formulary. Faced with competition from biosimilars, Humira is likely to drop out of the top 10 in 2024. In response to the decline of adalimumab, AbbVie has supported two new products in the field of autoimmune diseases: the IL-23 monoclonal antibody Skyrizi (risenkizumab) and the JAK1 inhibitor Rinoq (upadatinib). These two new products will both reach a growth rate of more than 50% in 2023, with a total revenue of 117$3.3 billion. Pfizer: Covid vaccine comirnatyIn 2023, Pfizer's total revenue will be $58.5 billion, down 41% year-on-year, and the direct impact on performance is the sharp contraction in sales of the new crown vaccine Comirnaty and the new crown oral drug Paxlovid. Comirnaty will achieve revenue of $12.2 billion in 2023, including $2.4 billion in the United States, although it is down 70% year-over-year. The new crown oral drug Paxlovid revenue 12US$7.9 billion, down 92% year-on-year; The CDK4 6 inhibitor palbociclib yielded 47US$5.4 billion, down 6% year-on-year. In May 2023, Pfizer's new RSV (respiratory syncytial virus) vaccine, Abrysvo, was approved for marketing in the United States, with annual revenue of 8$900 million, becoming the next few potential items. 
Regeneron: AfliberceptRegeneron (REGN) sales for the full year 2023 were 131$200 million, an increase of 8% year-over-year. , and its key product, Eylea, had sales of 92$1.5 billion, down 4% year-on-year. Among them, sales in the United States were 58$8.5 billion, with sales outside the U.S. of $34.4US$9.5 billion (sold by Bayer, with a share of the regeneron shares). Bayer has yet to report its 2023 earnings report, with sales of 34 percent for its eylea$5.9 billion. 
In response to the onslaught of aflibercept biosimilars, Regeneron and Bayer have developed a high-dose 8mg version of aflibercept, with an extended interval from once every 2 months to every 4 months. In August 2023, the FDA approved aflibercept 8mg for wet age-related macular degeneration. In China, this version of the product has been declared for marketing. 
Gilead: BickenpronoBiktarvy is an antiretroviral drug manufactured by Gilead Corporation in the United States for human immunodeficiency virus (HIV) infection. Biktarvy was approved by the U.S. Food and Drug Administration (FDA) in 2018, and in 2022, Biktarvy generated revenue of $10.4 billion, with a compound growth rate of 7216%。According to the Top Product Forecasts for 2024, the product's revenue in 2023 is close to $12.5 billion, up 21% year-over-year. Johnson & Johnson: UstekinumabJohnson & Johnson's full-year 2023 results reached $85.2 billion, up 65%, and its blockbuster autoimmune product ustekinumab (Stelara) revenue was $10.8 billion, a year-on-year increase of 117%, which is the first time that the product has broken the $10 billion mark. Ustekinumab is a drug targeting IL-12 and IL-23, which was approved in the United States and China in 2008 and 2017, respectively, for the use of ** psoriasis, psoriatic arthritis, ulcerative colitis and Crohn's disease and other autoimmune diseases. Ustekinumab is the main driver of growth in Johnson & Johnson's autoimmune segment, but its U.S. patent protection expires in September 2023, and it will soon face competition from biosimilars from Biocon Biologics, Alvotech, Amgen and others, and the launch of generic drugs will inevitably cause its sales to decline. Johnson & Johnson introduced nipocalimab, an FCRN monoclonal antibody from Momenta, to develop myasthenia gravis, neonatal hemolytic disease, systemic lupus erythematosus and other diseases. BMS: nivolumabIn 2023, Bristol-Myers Squibb (BMS) will have a total revenue of 4500.6 billion US dollars, down 2% year-on-year, and its PD-1 inhibitor opdivo (nivolumab) sales were 9 billion US dollars, an increase of 9% year-on-year. Together with Ono Pharmaceutical's $1 billion in the Japanese market, nivolumab's full-year sales in 2023 will reach $10 billion for the first time. Nivolumab is the biggest competitor of K drug in the PD1 PD-L1 field. Up to now, the FDA has approved more than 20 indications for 11 cancer types of nivolumab, and 9 indications have been approved in China, covering lung cancer, head and neck cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, colorectal cancer, urothelial cancer, melanoma, Hodgkin lymphoma, pleural tumors, etc. Currently, Opdivo is also actively exploring the combination of O+Y and PD1+LAG3**. In recent years, BMS has faced great challenges from the patent cliff: the core patents of lenalidomide have expired in 2019, most of the other patents will expire around March 2022, apixaban (2026, 2031) and drug O (2028) will also lose their patent exclusivity in recent years, and nivolumab will also face patent expiration in the United States in 2028. The Age of Ten Billion DollarsRecently, Nature Reviews Drug Discovery released the "Top Product Forecasts for 2024" analyst business analysis newsletter "Top Product Forecasts for 2024"* the top 10 drugs that will lead the global pharmaceutical market in 2024. 
Although the world is trying to regulate drugs**, it cannot prevent the drug market from entering the era of 10 billion dollars. In addition to the above 10 models, there are several drugs that are just one step away from the 10 billion dollar club. In 2023, Johnson & Johnson's CD38 monoclonal antibody DARAZALEX (daratumumab) increased by 22% in sales of $9.7 billion; Futai Pharmaceutical's cystic fibrosis drug Trikafta Kaftrio sales of $8.9 billion, up 16%; Merck's HPV vaccine Gardasil Gardasil 9 (Jiadaxiu) sales of 88$8.6 billion, an increase of 29%. These three products are still maintaining double-digit growth on the basis of approaching the threshold of 10 billion, and it seems that it is only a matter of time before sales exceed 10 billion US dollars by 2024. In 2023, the FDA approved 51 new drugs for a wide range of diseases, from Alzheimer's disease and cancer to migraines, menopausal symptoms and postpartum depression, many of which have achieved a considerable degree of breakthrough and innovation. February** Dynamic Incentive Program