As multinational pharmaceutical companies have successively disclosed their Q1 2024 financial reports, the rankings of global blockbuster drug sales for Q1 have been revealed. In Q1 this year, the sales of 13 global blockbuster drugs exceeded 2 billion US dollars. MSD's pembrolizumab, Keytruda (commonly known as "K-drug," Chinese trade name: Keruida), still firmly tops the list, while Novo Nordisk's semaglutide, Ozempic (for glycemic control, Chinese trade name: Novotai), ranks second. Bristol-Myers Squibb/Pfizer’s anticoagulant apixaban, Eliquis (Chinese trade name: Aileto), ranks third. This ranking remains unchanged from the 2023 global blockbuster drug sales ranking.
Other best-selling drugs in the TOP10 include Dupixent (Chinese trade name: 达必妥) by Sanofi/Regeneron, Biktarvy (Chinese trade name: 必妥维), a compound preparation by Gilead, Darzalex by Johnson & Johnson, Trikafta (a triple combination preparation) by Vertex Pharmaceuticals, Stelara (Chinese trade name: 喜达诺) by Johnson & Johnson/Mitsubishi Tanabe, Opdivo (commonly known as "O drug", Chinese trade name: 欧狄沃) by Bristol-Myers Squibb/Ono Pharmaceutical, and Humira (Chinese trade name: 修美乐) by AbbVie/Eisai.
In addition, the sales of Regeneron/Bayer's Aflibercept Eylea (Chinese trade name: Alia), MSD's nine-valent HPV vaccine Gardasil (Chinese trade name: Gardasil), and AbbVie's Risankizumab Skyrizi in the first quarter of this year also exceeded 2 billion US dollars.
Humira Sales Plummet, K Drug Ascends to "Top Drug" Throne
Pembrolizumab (K drug) is MSD's core anti-tumor drug, which was approved for marketing in the United States in September 2014. It has become the world's best-selling PD-1 monoclonal antibody in recent years, with over 30 approved indications. It is not only the PD-1 monoclonal antibody with the most approved indications covering cancer types, but also the immune checkpoint inhibitor with the most comprehensive layout for lung cancer indications. In 2018, the K drug was approved for marketing in China. From $1.402 billion in 2016 to $20.937 billion in 2022, the K drug took only seven years since its launch. Since its market debut, the sales growth of the K drug has basically remained above 20%. Industry analysis points out that the strong growth momentum of the K drug is mainly related to its continuous penetration and maintenance of significant market advantages in key cancer types such as non-small cell lung cancer and triple-negative breast cancer.
The competition for the "best-selling drug" in 2022 garnered significant attention, with MSD's Keytruda (K药) narrowly losing to AbbVie's blockbuster drug Adalimumab (Chinese trade name: Humira/修美乐) at $20.937 billion. In 2023, Keytruda achieved a sales revenue of $25.011 billion with a growth rate of 19.5%, surpassing Humira to claim the top spot. Humira, on the other hand, fell to fourth place with sales of $14.404 billion (a year-on-year decline of 32.2%).
In the first quarter of this year, Keytruda (K药) ranked at the top with sales of $6.947 billion, while Humira (修美乐) dropped to 10th place with sales of $2.27 billion.
The significant decline in Humira's sales is related to the encirclement of biosimilars. The composition/active ingredient patents for Humira expired in the United States and the European Union in 2016 and 2018, respectively, prompting pharmaceutical companies to join the race in developing adalimumab. In the EU market, in 2019, Humira faced the launch of four biosimilars, resulting in a sales drop of nearly $800 million from its peak period. In China, apart from the original drug Humira, seven locally produced adalimumab biosimilars have been approved for marketing, with an additional adalimumab biosimilar from the Wuhan Institute of Biological Products under China National Pharmaceutical Group (Sinopharm) submitted for marketing approval. It can be foreseen that Humira’s sales may further decline.
However, the time left for Keytruda to dominate the market alone is also limited. By 2028, Keytruda's core patent will lose protection, and once the patent expires, Keytruda will face a situation similar to that of Humira.
Semaglutide Shows Strong Growth Momentum, Development of Multiple Innovative Drugs Accelerates
In the past two years, Novo Nordisk's semaglutide has drawn significant attention. To date, there are three semaglutide products on the market: Ozempic (injectable antidiabetic), Wegovy (injectable weight-loss medication), and Rybelsus (oral antidiabetic). In the global market, semaglutide has gained immense popularity within the GLP-1 drug class since its approval for weight-loss indications, experiencing a supply shortage for nearly a year. In 2022, the total sales of semaglutide surpassed $10 billion for the first time, reaching approximately $21.2 billion in 2023, marking an 88.8% year-over-year increase.
Due to the limited supply of semaglutide Wegovy (for weight loss indications), many obese patients have started using semaglutide Ozempic (for diabetes indications) as a substitute, leading to drug shortages for diabetic patients. As a result, Novo Nordisk has had to implement various restrictions to prioritize the drug supply for diabetic patients. These restrictions are expected by Novo Nordisk to last until 2024. In China, the weight loss indication of semaglutide has been submitted for marketing approval, and Novo Nordisk is expected to receive approval this year.
In China, companies such as Sinopharm Dongfeng, Jiuyuan Gene, Hanmi Pharmaceuticals, Livzon Group, and CSPC are developing biosimilars of semaglutide. Among them, Jiuyuan Gene's semaglutide marketing application was accepted by the National Medical Products Administration in April this year, becoming the first reported biosimilar of semaglutide in China. Several other pharmaceutical companies also have related products entering Phase III clinical trials.
In addition to the threat from biosimilars, semaglutide also faces competition from other innovative drugs. For instance, Eli Lilly's tirzepatide has initiated a head-to-head clinical trial with semaglutide for weight loss indications, directly challenging semaglutide. On November 8, 2023, tirzepatide received approval for weight loss indications in the United States. In August 2023, the application for tirzepatide’s weight loss indication was accepted in China.
Mashiduo Peptide, a weight-loss and glucose-lowering drug co-developed by Innovent Biologics and Eli Lilly, has reached the primary endpoint in the Phase III clinical trial (DREAMS-2) conducted among Chinese patients with type 2 diabetes. The weight-loss indication has also entered Phase III clinical trials.
According to the Dingxiangyuan Insight database, there are over 20 clinical research projects globally targeting GLP-1 class obesity treatment drugs.
Apixaban ranked third in global sales in the last year and the first quarter of this year.
In 2022, the global sales of apixaban from Pfizer/Bristol-Myers Squibb totaled $18.269 billion. In 2023, with a slight growth of only 3.7%, it achieved sales of $18.953 billion, ranking third. In the first quarter of this year, apixaban still ranked third with sales of $3.72 billion.
Apixaban was jointly developed by Bristol-Myers Squibb and Pfizer. It was first approved for marketing in the European Union in May 2011. In December 2012, it was approved by the U.S. Food and Drug Administration (FDA) for sale in the United States; in January 2013, it was approved by the former State Food and Drug Administration to enter China.
Since the launch of Apixaban, its global sales have shown strong growth, attracting significant attention from numerous pharmaceutical companies. In recent years, it has faced a "siege" from generic drugs, including in China, where multiple global pharmaceutical firms, including Chinese companies, have launched patent challenges against Apixaban. In China, which is overseen by Bristol-Myers Squibb for sales, companies such as Dongyang Bright Pharmaceutical, Huahai Pharmaceutical, and Nanjing Runno have initiated patent challenges and successfully accelerated the market entry of generics. As a result, the price of Apixaban in China has significantly decreased, and the market share of the original drug has been greatly squeezed. According to the Dingxiangyuan Insight database, to date, more than 30 local companies, including Sailong Pharmaceutical, have received approval for their generic versions of Apixaban.
In the U.S. market, in 2017, Bristol-Myers Squibb and Pfizer filed patent infringement lawsuits against 25 generic drug companies that had submitted applications to the FDA for market approval. A key composition patent for apixaban was extended by the U.S. Patent and Trademark Office until November 2026, while another formulation patent does not expire until 2031. However, in December 2019, the FDA had already approved the first generic drug applications from two companies, and in 2022, Huahai Pharmaceutical's Abbreviated New Drug Application (ANDA) for apixaban tablets also received tentative approval. Once the original drug patents expire, these generics will be eligible for sale in the U.S. market.
In the European market, according to information released by the Intellectual Property Protection Center in September 2023, Bristol-Myers Squibb successfully removed generic drugs from the Dutch market in a dispute involving apixaban. France's Judicial Court also rejected Teva's request to invalidate a patent, while the UK Court of Appeal confirmed the invalidation of the apixaban patent. In other European countries such as Italy and Norway, the patent battle over apixaban continues.
Reporter Wang Kala from The Beijing News
Proofread by Lu Qian