Source of this article: Times Finance Author: Zhang Yuqi
In the past month, a number of GLP-1 star products have been approved in China.
On June 25, the Danish pharmaceutical giant Novo Nordisk announced that the State Food and Drug Administration (NMPA) recently officially approved the new indication of semaglutide injection (trade name: Novo Synopon) for marketing, which is suitable for long-term weight management of adult patients on the basis of diet control and increased physical activity, and the patient's initial body mass index (BMI) is greater than or equal to 30kg/㎡ (obesity); or between 27 kg/㎡ and 30 kg/㎡ (overweight), and at least one weight-related comorbidity, such as hyperglycemia, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease.
On the same day, Sino Biopharma (01177. Liraglutide Injection (trade name: Belerine) developed by Chia Tai Tianqing, a subsidiary of Chia Tai Tianqing, has been approved by the State Food and Drug Administration for the control of blood sugar in adult patients with type 2 diabetes.
Earlier, at the end of May, Eli Lilly's major product tirpatide injection (trade name: Mu Fengda) was approved for marketing in China, which is suitable for adult patients with type 2 diabetes who are still poorly controlled with blood sugar after receiving metformin and/or sulfonylureas on the basis of diet control and exercise.
China Merchants Securities (Hong Kong) Research Report predicts that by 2030, the market size of GLP-1 drugs for type 2 diabetes and obesity will exceed the US$100 billion mark. In addition, GLP-1 leading companies are developing indications other than type 2 diabetes and obesity, including cardiovascular risk, metabolic dysfunction-associated steatohepatitis (MASH), chronic kidney disease (CKD), sleep apnea, and neurodegenerative diseases.
A number of interviewees said at the "GLP-1 Drug Industry Leaders Closed-door Private Meeting" held on June 28 that in view of the reform and rapid development of the GLP-1 track, more consideration should be given to how to use innovative breakthroughs to solve involution, such as changes from the new mechanism and technology level, in order to truly solve clinical needs.
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The involution of the GLP-1 track intensified
GLP-1, also known as glucagon-like peptide-1, is a peptide hormone encoded by the human glucagon gene and secreted by intestinal L cells, which can promote the synthesis and secretion of insulin, suppress appetite, delay the emptying of gastric contents, etc. In the 90s of the 20th century, scientists found that GLP-1 can promote insulin secretion, and with the deepening of research, scientists realized that GLP-1, which plays a physiological role in the human body, can bind to specific receptors on the surface of pancreatic islet β cells and a variety of other cells to exert hypoglycemic effects.
According to incomplete statistics from Times Finance, since the launch of the first GLP-1 receptor agonist drug exenatide in 2005, more than 10 GLP-1 receptor agonist products have been launched worldwide. Among them, the drugs approved for marketing in China include benaglutide, exenatide, lisinatide, liraglutide, exenatide microspheres, dulaglutide, pegylated loceglutide, semaglutide, etc.
Although a number of GLP-1-related products have been approved before the birth of semaglutide, they are not as popular as this "latecomer". With semaglutide being listed and selling well in many countries around the world, the involution of the GLP-1 track is being upgraded day by day.
In December 2017, semaglutide was officially approved by the U.S. Food and Drug Administration (FDA) for marketing as an adjunct to dietary control and exercise to improve blood sugar control in patients with type 2 diabetes. This is the first time that semaglutide has been approved in the global market. Since then, semaglutide has swept the global diabetes market and weight loss market, and up to now, there are 3 dosage forms of semaglutide in the US market, namely Ozempic (hypoglycemic drug for injection), Wegovy (weight loss drug for injection) and Rybelsus (oral hypoglycemic drug).
In China, both the diabetic version and the weight loss version of semaglutide injection have been approved, and semaglutide tablets (trade name: Novoxin) were also approved in China in late January this year for the treatment of type 2 diabetes.
Today, semaglutide has become an important engine for Novo Nordisk's performance growth. According to Novo Nordisk's quarterly report this year, semaglutide supported about 2/3 of Novo Nordisk's revenue, and the three related products achieved a total revenue of 42.2 billion Danish kroner (equivalent to about 6.081 billion US dollars).
Another GLP-1 star product, tirpatide injection, has also been approved in China, and in May and November last year, its hypoglycemic version Mounjaro and slimming version Zepbound were approved by the US FDA for marketing, respectively, and have also sold well since their launch. According to the financial report, in the first quarter of 2024, tirpatide contributed $2.324 billion in revenue to Eli Lilly, accounting for about 26% of total revenue.
Shen Weijun, a senior researcher at Shenzhen Bay Laboratory and director of the Center for Translational Medicine, said at the above event, "Especially in the field of GLP-1, the industry and enterprises have felt its heat, and this track is very volatile. According to Shen Weijun, at home and abroad, there are more than 300 pipeline projects in the clinical stage of the GLP-1 track, and 15 have been approved, of which 9 are real innovative drug molecules. In addition, GLP-1 has more than 40 pipelines of dual-target projects and more than 20 three-target projects, and the popularity of the track is increasing dramatically.
Pharmaceutical companies have launched related projects one after another, stemming from their optimism about the prospects of the GLP-1 drug market.
The report from Goldman Sachs mentions that by 2028, as many as 68 million Americans could take GLP-1 drugs, or about 20% of the U.S. population.
Chen Xiaoxin, co-founder and president of Zhongsheng Ruichuang, said at the above event that metabolic diseases have huge unmet needs and market space. "According to the IDF Global Diabetes Map (10th Edition), there were an estimated 537 million people living with diabetes worldwide in 2021, 643 million by 2030 and 783 million by 2045." Chen Xiaoxin said.
After Simei, how does the industry innovate?
Nowadays, more and more companies are pouring into the GLP-1 track, and the leading companies have also entered the harvest period, especially under the strong monopoly of the "duopoly" of Novo Nordisk and Eli Lilly, the difficulty of latecomers to stand out from the encirclement has increased sharply.
On July 3, Times Finance searched the wisdom buds new drug intelligence database and found that a total of 2,594 clinical trials were retrieved with the keyword GLP-1R as an example, including semaglutide, liraglutide, dulaglutide, etc., and the indications include type 2 diabetes, obesity, non-alcoholic steatohepatitis, and the participating companies include Novo Nordisk, Eli Lilly Pharmaceutical, Hengrui Pharmaceutical, Tonghua Dongbao and many other companies.
Jiang Shibo, director of the Institute of Pathogenic Microbiology of Fudan University, said at the above event, "At present, the involution problem of the GLP-1 track is the same as the PD-1 track of the year. In order to advance the entire field of peptides and GLP-1, it is still hoped that enterprises and R&D personnel will consider target innovation and not be limited to one direction. ”
In the face of involution, the situation of small and micro enterprises is even more difficult. Luo Hua, general manager of Chongqing Punovi, said frankly at the above event, "GLP-1 and the entire peptide field are very hot, but they are also very volatile, and a small company like us will not be able to go on its own." ”
"In this track, we must first clarify the differentiated development, including the last weight loss drug market in GLP-1, not the more weight loss after medication, the better, but to have a degree, to consider the speed of weight loss and the effect of weight loss to achieve a balance. At the same time, we also need to consider the side effects of the drug, for example, we found that the multi-target effect may be better when we do animal experiments, but it may also bring a certain degree of side effects, and this change is excessive. Therefore, in research and development, it is necessary to pay attention not only to the effect of the drug, but also to consider the side effects of the drug. Luo Hua pointed out that "in terms of differentiated development, we can improve and do innovative tests in terms of adverse reactions, and consider how to reduce adverse reactions and increase the adaptability of the population." In addition, there is room for innovation in the improvement of dosage forms, quality control, and improvement of bioavailability. ”
In the upstream and downstream industrial chain of GLP-1, companies are not only rolling drugs, but also rolling production capacity and costs. As the demand for GLP-1 products in the diabetes market and weight loss market surges, companies continue to expand their production capacity.
Recently, Novo Nordisk announced an investment of $4.1 billion to expand the company's manufacturing capacity in the United States, and it plans to build a second filling and finishing manufacturing plant in Clayton, North Carolina, to enhance its ability to produce semaglutide-related drugs "Wegovy" and "Novotec" (Ozempic).
Su Xianbin, a professor at Nanjing University of Technology, said in the above event that drugs need a lot of innovation from 0~1, and innovation at the process level is also very important. "If the process is improved and the production capacity is increased, it can also reduce the cost and make the people afford to use the drug." Su Xianbin further said.
Wang Qunjie, the founder of AGEBOYA, further explained how to improve efficiency and reduce costs from the aspects of process improvement and differentiation. "From the perspective of our upstream enterprises, we are more about providing a tool for everyone, which can improve the efficiency and bring value to the finished medicine. Specifically, from the perspective of the peptide field, this improvement process is to help enterprises achieve the purpose of differentiation, or assist enterprises in customizing or developing new materials. ”