In recent years, the development of peptide drugs has shown a high degree of vitality, and many large pharmaceutical companies and start-ups are committed to exploring this field. During 2015-2019, FDA approved 208 new drugs, including 15 peptides or molecules containing polypeptides, accounting for 7% of the total new drugs.

Drug containing polypeptide approved by FDA in 2015-2019 (photo source: reference [4])

Peptide conjugation with antibodies, oligonucleotides and various toxins has been widely used in the development of new drugs. From 2015 to 2019, five new peptide drugs were approved in oncology, two of which were antibody coupled drugs; three in metabolism and two in endocrine, which were the most common indications of peptide drugs. In addition, we are pleased to see that peptide drugs targeting cardiovascular diseases, gastrointestinal diseases, bone diseases, skin diseases and sexual dysfunction have been successfully marketed. In the broad field of disease treatment, peptide drugs show a vigorous development trend.

In addition, scientists continue to explore more convenient and effective preparation technology and delivery methods. For a long time, peptide drugs mainly rely on injection. Now, in addition to classic injections, microspheres, oral preparations and other dosage forms have broken through the barriers of research and development, allowing more choices of peptide drug preparations.

In 2017, somaluptide injection for improving blood glucose control in adult patients with type 2 diabetes was launched. Thanks to the continuous technological breakthroughs in peptide preparations in recent years, oral somaluptide was approved by FDA in September 2019 and became the first oral glucagon like peptide-1 (GLP-1) receptor agonist in the world. In the field of diabetes treatment, which has long been a red sea, oral peptide preparations have broken through the tight encirclement and successfully promoted to the era of 2.0.

In the past, the oral administration of polypeptide preparations was inconceivable. Enzymes in the digestive tract were fatal to many polypeptide molecules. In addition, the intestinal mucosal barrier was insurmountable for common polypeptides. With the help of a variety of osmotic enhancers and intestinal enzyme inhibitors, peptide drugs have been able to penetrate intestinal mucus and cells successfully and realize oral administration. Somaluptide is a traditional linear structure and does not have any oral bioavailability. However, it can penetrate intestinal mucosal cells and absorb into blood in a short time after mixing with sodium caproate (SNAC). Although the bioavailability of oral polypeptide drugs still needs to be further improved, it is still the general trend to enhance the treatment compliance of patients.

One hundred years of potential

Up to now, peptide molecules have been used in the treatment of diseases for more than 100 years, but it is still in the ascendant.

Traditional peptide hormone drugs are still indispensable in clinical practice; antibacterial peptides are also expected in the field of anti infection; in the field of anti-tumor, peptide related drugs have been approved one after another in recent years, occupying a place; in addition, as effectors of cell signaling pathway, peptide cytokines bring new ideas for the research of more diseases. The vast space is waiting for exploration and opening.