Teduglutide is a GLP-2 analogue consisting of 33 amino acids Teduglutide is produced using a strain of Escherichia coli modified by DNA recombination technology, which differs from GLP-2 by one amino acid (alanine replaced by glycine). The significance of this substitution lies in the fact that the action time of tiltrotide is longer than that of endogenous GLP-2, and it is more resistant to the protein hydrolysis of DPP4.

The half-life of Teduglutide is longer than GLP-2 (Teduglutide is 2-3 hours, while GLP-2 is 7 minutes). After subcutaneous administration, Teduglutide has high bioavailability, indicating that compared to natural GLP-2, Teduglutide has enhanced biological activity.

Teduglutide was first approved for marketing in the European Union in 2012, and subsequently approved for marketing in the United States and Japan for the treatment of short bowel syndrome. In 2013, Shire published a 52 week clinical study data showing that for patients with short bowel syndrome and intestinal failure, the efficacy of Teduglutide can be maintained for 52 weeks, and its safety is sufficient to consider long-term use.

Teduglutide has been clinically proven to increase the residual intestinal villus height and crypt depth in SBS patients, promote the recovery of gastrointestinal absorption function in SBS patients, reduce dependence on PN, and even significantly increase the proportion of patients who completely get rid of PN.

About Short Bowel Syndrome

Short bowel syndrome (SBS) refers to a syndrome characterized by a significant reduction in the effective absorption area of the intestine after extensive small bowel resection or displacement due to various reasons. The remaining functional intestinal tract cannot maintain the patient's nutrition or children's growth needs, and is mainly characterized by diarrhea, acid-base and water/electrolyte imbalances, as well as various nutrient absorption and metabolism disorders.

SBS is a rare disease with a heavy disease burden. Patients can develop severe water and electrolyte imbalances, deficiencies in macronutrients and micronutrients, bile stasis, liver complications such as intestinal failure associated liver disease (IFALD), kidney stones, renal failure, excessive bacterial proliferation in the small intestine, metabolic bone disease, and various complications related to catheterization (such as catheter-related infections, thrombosis, and catheter rupture), which seriously affect the quality of life of patients.

Teduglutide R&D: Impurities Synthesis

Currently, peptide drugs such as Teduglutide have become one of the hotspots in global drug development. Peptide drugs have become the troika driving the market in the treatment of rare diseases, tumors and diabetes, especially in the treatment of diabetes.

At present, chemical synthesis technology is still the mainstream method for producing peptide drugs. From early solution synthesis technology to later solid-phase peptide synthesis process, after years of technological innovation, the synthesis process has become mature. The main steps of chemical synthesis of peptide chains include resin loading, deprotection of functional groups, activation and cross-linking reactions, and peptide chain cleavage. In this process, the steps of deprotection, activation, and cross-linking are the most prone to impurities, so these steps are usually considered the focus of quality control.

Active peptides are the material basis for the action of drugs, so quality control of active peptide raw materials (APIs) is crucial in the development of peptide drugs. Among them, controlling peptide related impurities is one of the core tasks of quality management. These impurities not only affect the quality and safety of clinical trial samples, but may also interfere with the evaluation of drug efficacy in the early stages of drug development. If the research on impurities is not sufficient, it may even lead to erroneous conclusions, resulting in research and development failure or delay.

Teduglutide and impurities are of great significance in the research and control of related impurities at various stages of development and production. Especially in the early stages of drug development, impurities may cause misjudgment due to their antagonistic effects or interference with drug efficacy. Therefore, it is recommended to use peptide raw materials from different sources in biological testing to ensure the accuracy of test results and eliminate the potential interference of impurities on drug efficacy evaluation.