The molecular weight of peptides is generally between small molecules and antibodies. Therefore, peptide drugs have unique advantages compared with small molecules and biological agents represented by antibodies, making them one of the important components in drug development.
Solid-phase synthesis is the current mainstream peptide synthesis process. The mass production of peptide drugs usually requires consideration of technical applications, production processes, production costs, quality management and environmental protection. At present, the solid-phase synthesis method is relatively mature, and most of the peptide drugs on the market use this process route.

GLP-1

At present, blockbuster peptide drugs are mainly concentrated in the field of diabetes. In 2022, the sales of semaglutide, dulaglutide, insulin aspart, insulin lispro, and insulin glargine will exceed US$2 billion. In addition to weight loss and diabetes, there are also many best-selling peptide drugs in other disease fields, involving many large pharmaceutical companies and biotechnology companies. In the field of oncology, the sales of Ipsen’s lanreotide and Novartis’ octreotide will both exceed US$1 billion in 2022. In addition, Novartis’s radioactive peptide targeted tumor treatment drug Pluvicto has been rapidly increasing its sales since it was approved by the FDA in March 2022. Sales in 2023 will exceed US$1 billion, ranking among the blockbusters. In the field of anti-infection, Pfizer’s Paxlovid has played an important role in the prevention and treatment of the new coronavirus. Sales in 2022 reached US$18.9 billion, becoming the best-selling small molecule drug that year. Rare diseases are also the main battlefield for peptide drugs. Glatiramer, developed by Teva and launched in 1996, was once the largest variety of peptide drugs. Its global sales reached US$4.237 billion in 2014 and is used to treat multiple sclerosis (MS). On June 28, 2023, glatiramer acetate injection (trade name: Gupaisone) was officially approved in China and is suitable for the treatment of adult patients with relapsing multiple sclerosis (MS).

GLP-1 (glucagon-like peptide-1) is an incretin hormone produced in the intestine that stimulates insulin secretion to lower blood sugar levels. GLP-1 receptor agonists (GLP-1 RA) have become important drugs in the treatment of type II diabetes due to their unique pharmacological effects and good safety. At the same time, in recent years, it has also shown good therapeutic effects in the fields of obesity, cardiovascular disease, etc., and its application prospects are very broad.

Of course, GLP-1 peptide drugs have received the most attention in the past two years. GLP-1 agonists work primarily by stimulating the release of glucose-dependent insulin from pancreatic islets. Secondly, these drugs can also slow gastric emptying and suppress appetite. According to data from the U.S. Centers for Disease Control and Prevention (CDC), approximately 35 million Americans suffer from type 2 diabetes, and there are approximately 460 million diabetic patients worldwide, accounting for 63% of the global population. This figure reflects the huge size of the anti-diabetic drug market. Initially, natural incretins were not suitable candidates for drug development, but as the need for antidiabetic drugs increased, researchers eventually developed GLP-1 receptor agonists into drugs. Semaglutide, as a representative product of current GLP-1 agonists, replaces glycine with 2-aminoisobutyric acid (Aib) at position 2 and connects octadecanedioic acid to the Lys-26 side chain. Effective transformation of natural peptides was achieved. This modification enhances its resistance to the proteolytic enzyme DPP-4 and highly binds to serum albumin through the fatty acid moiety, extending the half-life in the human body to approximately 7 days.