**: Briana***
Author: April Rain.
Peptides are usually composed of 10-100 amino acids, and the molecular mass is generally less than 10,000 daltons. Because the molecular weight of peptides is between small molecules and biological products, the formation of peptide drugs has the characteristics of high selectivity and low concentration, thereby reducing toxicity
In recent years, with the approval of semaglutide, peptide drug research and development has become one of the hottest drug development fields in the world. According to public data, as of the beginning of 2023, there are nearly 180 peptide drugs on the market worldwide, with indications including diabetes, obesity, tumors, cardiovascular diseases, and hepatitis
From the perspective of targets, involving GLP-1, Insulin, HER2 and other targets, according to the statistics of pharmaceutical intelligence data, whether in the world or China, INS, GLP, etc. are the top three targets in peptide drug research. At present, the hottest target is GLP-1.
Fig.3 Peptide drug targets.
Pharmaceutical Intelligence Data.
GLP-1 - the most popular target of peptide drugs at present
GLP-1 belongs to the incretin class of drugs, which is a cerebro-intestinal peptide in ileal endocrine, and is currently mainly used as a target for type 2 diabetes drugs. In addition, because GLP-1 can inhibit gastric emptying and reduce intestinal peristalsis, it has a weight-loss effect, and has become a new choice for weight-loss invasive drugs.
According to the data of Pharmaceutical Intelligence, there are currently more than 200 studies on GLP-1 targets in different clinical stages. Table 1 shows some of the peptide GLP-1 drugs that are currently approved and in the clinical stage. Representative drugs that have been approved are Semaglutide from Novo Nordisk and Tirpatide from Eli Lilly.
Table 1 Some GLP-1 target peptide drugs.
Data**: Pharmaceutical intelligence data.
According to Novo Nordisk's 2023 Q3 financial report, semaglutide has a total revenue of 1002 in the first three quarters of 2023DKK 2.2 billion, or about USD 14.2 billion, accounts for 60% of Novo Nordisk's total sales. According to Eli Lilly's 2023 Q3 financial report, tirpatide had a total revenue of 29 in the first three quarters of 2023$5.7 billion, sales continued to rise sharply;With the approval of the first indication, and compared with semaglutide, tirpatide still has certain advantages, and the sales of tirpatide may grow more rapidly.
In addition to the approved products, there are also several GLP-1 products under development that deserve everyone's attention.
NN1535 is a combination of long-acting insulin icodec and semaglutide for the treatment of type 2 diabetes mellitus, which is currently in the clinical stage. For the members of this combination combination, icodec insulin has been structurally modified and optimized to extend the half-life to 196 hours, and semaglutide can reach more than 7 days, so if NN1535 is finally approved, the dosing interval will not be less than 7 days, which will improve patient compliance and glycemic control.
IBI362, co-developed by Eli Lilly and Innovent, and LY3437943, developed by Eli Lilly, have both shown good results, and LY3437943 is the world's first GLP-1R GIPR GCGR triple target inhibitor.
According to public information, the revenue of GLP-1 drugs in the first three quarters of 2023 exceeded 25 billion US dollars, equivalent to 180 billion yuan. Among them, diabetes still occupies an absolute advantage, and the sales of GLP-1 drugs sold in the first three quarters of 2023 account for about 81%. According to Novo Nordisk, the current prescription volume of GLP-1 drugs in the global diabetes market accounts for only about 6%, and only 33%, so with the gradual increase in the market penetration rate of GLP-1 drugs, the GLP-1 market will also increase steadily in the future.
Fig. 1 GLP-1 drug market.
Ref. 1
Due to the potential market prospect of GLP-1 and the increasingly hot weight reduction benefits, the competition in the GLP-1 R&D track has been very fierce. In order to seek maximum competitiveness, it is an unstoppable trend to seek differentiated development in peptides, and for this reason, scientists are not limited to just one target.
INS targets, the "last line of defense" for diabetic patients
Insulin (INS) is a common diabetic medication and is a hormone secreted by the body. At present, there are many kinds of insulin used in clinical practice, and the onset time, duration of action, and administration mode of different types of insulin are also different. Insulin, as the most direct and effective means, is the "last line of defense" for diabetes. According to the data of pharmacologics, there are currently more than 30 insulins under development.
It is worth noting that insulin is gradually transitioning from daily injections to weekly injections, and there are currently two weekly insulin formulations in the world that are in phase 3 or above clinical trials.
Table 2 Weekly insulin preparations.
Data**: Pharmaceutical intelligence data.
Among them, Novo Nordisk's enco insulin is the fastest in research as a weekly dose, and is currently in the registration application stage. According to public information, the insulin has a half-life of an astonishing 196 hours after structural modification and optimization.
It is worth mentioning that compared to the control group of insulin glargine and insulin degludec, insulin eco showed non-inferiority. In terms of safety, no difference in the frequency of hypoglycemia was noted.
Table 3 Clinical data of insulin enco.
Landscape orientation is recommended**).
Compiled by the official website of each company.
The second is Eli Lilly's LY-3209590, which is currently in clinical development. Clinical data showed that LY-3209590 also demonstrated non-inferiority compared to the control group of insulin degludec. In addition, LY3209590 has shown a better safety profile, which may help reduce the probability of hypoglycemia.
The third is GZR4 independently developed by Gan & Lee Pharmaceutical, compared with the above two, although GZR4 is only in the phase 2 clinical stage, it is the fastest research progress in this field in China.
According to the statistics of Yaozhi data, the sales of insulin in domestic sample hospitals in 2022 will be 1895.6 billion yuan, with sales of 72 in the first half of 20230.8 billion yuan, affected by centralized procurement, sales have continued to be the best in recent years, but as an indispensable drug in the field of chronic diseases, with the gradual listing of weekly preparations, the overall sales of insulin market are expected to rebound in great strides.
Figure 2 Sales of insulin in domestic sample hospitals.
Pharmaceutical Intelligence Data.
Other targets under development for peptide drugs
In addition to GLP-1 and INS, peptide drugs are also deployed in targets such as HER2, TPA and STR2.
Taking HER2 as an example, HER2 protein is an important protein in the human body, which has the role of participating in cell growth and regulation, but if the protein is overexpressed, it will lead to the rapid proliferation of cancer cells to form tumors, so HER2 is also an important target of cancer.
According to pharmacointelligence data, there are currently more than 350 HER2 target research projects, including 5 peptide class 1 new drugs.
At present, there are no approved drugs in this field, and the fastest progress is TPIV 110 and IMU-131, which are in Phase 2 clinical trials.
Table 4 HER2 target peptide drugs under development.
Data**: Pharmaceutical intelligence data.
For TPA targets, according to pharmacological data, there are currently more than 200 projects in different stages of research and development, including 7 peptide class 1 new drugs. However, the research progress of peptide drugs is relatively slow, due to the fact that the peptide drugs are relatively "old" and the development technology is difficult.
For STR2 targets, according to pharmacointelligence data, there are currently nearly 30 projects in different stages of research and development, including 6 peptide class 1 new drugs. Similar to TPA targets, research progress has been slow.
Summary
In summary, peptides, as a hot spot in the post-gene era, have been widely used in drug development. According to Frost & Sullivan data, the global peptide drug market size increased from US$56.8 billion in 2016 to US$62.8 billion in 2020, with a compound annual growth rate of 26%。The global peptide drug market size is expected to grow at a CAGR of 85%, which will reach $141.8 billion by 2030.
The market size of China's peptide drug industry has shown a rapid growth trend, rising from US$6.3 billion in 2016 to US$8.5 billion in 2020, with a compound annual growth rate of 8%, far exceeding the global growth rate, and the market size will further expand in the future, and is expected to reach US$18.2 billion in 2025, with a compound annual growth rate of 1704%。
Although looking at the world, there are already Moncs such as Eli Lilly, Novo Nordisk, AstraZeneca, Takeda, and Amgen that continue to carry out research and development in this field, and blockbuster drugs such as dulaglutide, semaglutide, semaglutide, and tirpatide have been born. Due to its potential drug development and market prospects, peptide drug development will continue to be favored, and we will wait and see.
References. 1]
2] Pharmaceutical Intelligence Data.
Proton Co., Ltd. provides global pharmaceutical companies, biotechnology companies, scientific research institutions, etc. with one-stop service solutions for small molecule drugs, peptides and oligonucleotides, biological macromolecules (MAB, ADC, etc.) and gene and cell drugs required for the whole life cycle from preclinical research to drug marketing, with R&D, production and operation sites covering China (Chongqing, Shanghai, Sichuan, Jiangsu, Jiangxi, Hubei), the United States, Slovenia, Belgium, Switzerland and Denmark. We are committed to being customer-centric and providing customers with excellent global, end-to-end CDMO services, so that good medicines can reach the public sooner.
Disclaimer: This article is the content of Yaozhi.com**, and the copyright of the text belongs to the original author, and the purpose is to convey more information, and it does not represent the position of Yaozhi.com. If it involves the content of the work, copyright and other issues, please leave a message on this platform, and we will delete it as soon as possible.