On December 18, Hansoh Pharma announced that it had entered into a global exclusive licensing agreement with Merck. Under the agreement, Merck is granted the global exclusive rights to develop, manufacture, and commercialize HS-10535, a preclinical oral small-molecule long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. Hansoh Pharma will receive an upfront payment of $112 million, with the total deal potentially reaching up to $1.9 billion. Under specific conditions of the licensing agreement, Hansoh Pharma may co-promote or exclusively commercialize the product in mainland China, the Hong Kong Special Administrative Region, and the Macao Special Administrative Region.
Why Has an Oral Small-Molecule GLP-1 Receptor Agonist Still in the Preclinical Stage Garnered Merck's Favor?
GLP-1 Receptor Agonists Spark a Sugar-Lowering and Weight-Loss Craze, with a Track Worth Tens of Billions Attracting Many Pharmaceutical Companies. As the Number of Developers of Common Injectable Formulations Increases, the Convenient Oral Formulation is More Differentiated but Not Without Considerable R&D Challenges. The Current R&D Directions are Mainly in Two Areas: Peptide Oral GLP-1 Receptor Agonists and Oral Small Molecule GLP-1 Receptor Agonists.
In the development of oral peptide GLP-1 receptor agonists, Novo Nordisk Medical Information previously stated that peptide drugs are usually administered via injection due to their poor oral bioavailability. The challenge with oral administration lies in overcoming various physical and physiological absorption barriers, including gastrointestinal enzyme degradation, entrapment by the gastrointestinal mucus layer, molecular barriers during paracellular or transcellular transport, and inter-individual variability. The successful development of oral semaglutide involved the addition of an absorption enhancer called SNAC, which facilitated the absorption of the large molecule semaglutide.
Screening small-molecule weight loss drugs targeting GLP-1 is another research and development direction. Many pharmaceutical companies are striving to find suitable small-molecule GLP-1 receptor agonists, but no products have been approved for marketing so far. According to the Insight database, companies such as Eli Lilly, Roche, Pfizer, AstraZeneca/Chengyi Biotech, Hengrui Medicine, Huadong Medicine, Salubris, and Wentai Medicine are actively promoting the development of oral small-molecule GLP-1 receptor agonists.
The orally administered small molecule GLP-1 receptor agonist with the most advanced development progress is Orforglipron from Eli Lilly. In January this year, the clinical trial registration and information disclosure platform of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) showed that Orforglipron, which Eli Lilly licensed from Chugai, has initiated a new Phase III clinical trial in China.
In September this year, the aforementioned information disclosure platform also showed that Hengrui Medicine has launched a Phase III clinical trial in China to evaluate the efficacy and safety of HRS-7535 compared with dapagliflozin in adult patients with type 2 diabetes. HRS-7535 is a novel oral small-molecule GLP-1 receptor agonist being developed for the treatment of type 2 diabetes and weight loss. In May this year, Hengrui Medicine licensed its proprietary GLP-1 product portfolio to U.S.-based Hercules Company in a deal worth over $6 billion, which included HRS-7535.
Pfizer is also developing oral small-molecule GLP-1 receptor agonists but has faced multiple setbacks, causing its R&D progress to lag. Among Chinese pharmaceutical companies, in addition to Hengrui Medicine, several others are also conducting clinical trials for oral small-molecule GLP-1 receptor inhibitors, including GSBR-1290 from Shuo Di Biologics, SAL0112 from Salubris, HDM1002 from Huadong Medicine, and RGT-075 from Rui Ge Pharma.
Reporter Wang Kala from The Beijing News
Proofread by Mu Xiangtong