The hypoglycemic drug market is turbulent again, and Fosun Pharma's 55 million yuan is lost

Recently, Fosun Pharma announced that its holding subsidiary Jiangsu Wanbang targeted SGLT-2 inhibitor Vanpagliflozin tablets is in the phase I clinical trial stage
.
Recently, Jiangsu Wanbang decided to terminate the clinical trial and subsequent development of the new drug
.
Up to now, the cumulative total R&D investment of this new drug project is approximately RMB 55.
23 million
.
At the same time, Hengrui Medicine also issued an announcement stating that the Class 1 chemical drug Proline Henggliflozin Tablets was approved for marketing, which is also the first domestically-made innovative SGLT2 inhibitor approved in China
.
Up to now, Hengrui has invested about 270 million yuan in research and development in related projects of Proline Henggliflozin
.
However, the oral hypoglycemic drug market is obviously not limited to these two actions.
Nanjing Chia Tai Tianqing's sitagliptin metformin sustained-release tablets, which are imitated by Category 3, have recently entered the stage of administrative approval and are expected to be approved for marketing in the near future
.
What kind of ups and downs have there been in this field of hypoglycemic competition? Millennium diabetes mellitus and century-old insulin diabetes are generally classified as “diabetes disease” or “diabetes mellitus” in Chinese medicine
.
The relevant symptom descriptions are evidence-based in the "Fifty-two Diseases Prescriptions" excavated in the Mawangdui Han Tomb, dating back about 2,200 years
.
In the later medical book "Huangdi Neijing", there is also a description of the symptoms of diabetes "three more and one less"
.
In the West, Hippocrates, known as the "father of medicine", also described many cases with massive urination and weight loss as clinical manifestations
.
However, it was not until the 18th century when Scottish doctor William Cullen was teaching at the University of Edinburgh that he formally proposed that dibetes should be divided into two types: diabetesinsipidus (diabetes insipidus) and diabetesmellitus (diabetes)
.
It was also from this time that scientific research on diabetes was gradually carried out.
However, the discovery of insulin, the first-generation treatment drug for diabetes, had to wait a hundred years ago.
In 1921, Canadian doctors Banting and Best used their summer vacation time to borrow Mike Professor Lauder's lab successfully extracts active insulin
.
Insulin was in clinical use just six months later
.
In October 1923, Banting and MacLeod won the Nobel Prize in Physiology or Medicine for the historic achievement of "discovering insulin", which was the fastest in the history of the Nobel Prize
.
Since then, insulin has continued to iterate
.
The first generation of insulin mainly comes from the pancreas of livestock such as pigs and cattle.
These insulins can easily activate the human immune response and cause human allergies.
Human insulin began to enter the market; at the end of the 20th century, people began to conduct in-depth research on the structure and physicochemical properties of insulin.
Scientists obtained the third generation insulin by modifying the peptide chain of insulin - insulin analogs, which can better simulate physiological insulin.
secretion, lower risk of nocturnal hypoglycemia plus refined and effective action in the human body
.
However, since insulin is a biological macromolecule and cannot be absorbed through the intestinal tract, the development of oral hypoglycemic agents has become an urgent need
.
Thousands of sails are exhausted, and metformin dominates At present, there are a variety of oral hypoglycemic drugs on the market, and metformin is the most dazzling star among them
.
As a product born at the same time as insulin, its fate is quite different from that of insulin
.
Metformin first originated from goat grass.
The chemical entity of metformin was reported in the literature in 1922.
Seven years later, its hypoglycemic effect was found in rabbits
.
But at that time insulin was in the limelight, and the role of metformin was hidden
.
Metformin was first used clinically in 1957, and it was approved for marketing in Canada 14 years later, and it would take nearly 40 years for metformin to be approved for marketing in 1994, nearly 40 years later
.
Today, although the mechanism of action of metformin is not clear, it is not only a basic drug in first-line drugs and drug combinations, but also a series of potential new effects such as treatment of hair loss, anti-aging, and weight loss have been found in long-term clinical use
.
According to the PDB database query, metformin and metformin combination drugs accounted for 32.
86% of the total oral hypoglycemic drugs in the sample hospital market in 2020
.
In the days when metformin was frozen, the new hypoglycemic forces sulfonylureas and glinides insulin secretagogues quietly emerged
.
In 1942, French physician Janbon discovered that sulfonamides can cause severe hypoglycemia in patients, opening the door to the structural study of sulfonylureas (SU)
.
In 1956, two German professors Franke and Fuchs successfully synthesized the first-generation sulfonylurea drug tolbutamide for the treatment of type 2 diabetes
.
In the following ten years, sulfonylureas have developed to the second generation, and glyburide, glipizide, gliclazide, glimepiride, etc.
have been discovered one after another, and they are still welcomed by doctors and patients
.
Both sulfonylureas and glinides act by stimulating the release of insulin from pancreatic β cells
.
When the above three drugs were fighting in the body, Bayer turned its attention to the external environment
.
In 1977, researchers at Bayer Corporation discovered acarbose from the secondary metabolites of pseudotetrasaccharides of the active actinomycetes, which mainly inhibited α-glucosidase to delay the decomposition of starchy foods into glucose in the intestinal tract.
to function
.
However, because the consumption of starchy foods is not high among European and American people, Bayer has to vigorously promote it in East and Southeast Asia, where rice and noodles are the staple food
.
Because of this, acarbose entered the Chinese market in 1994, and was approved by the US FDA in 1995
.
In the century-old struggle against diabetes, it was discovered that glucagon-like polypeptide-1 (GLP-1) can promote the release of insulin, and the development of GLP-1 receptor agonists was initiated
.
In 2009, a series of glucagon-like peptide-1 (GLP-1) analogs such as liraglutide and exenatide were launched
.
On the other hand, GLP-1 is easily degraded by dipeptidyl peptidase-4 (DPP-4) in vivo.
In order to solve this problem, sitagliptin, vildagliptin, etc.
were launched around 2007.
DPP4 inhibitors
.
The SGLT2 inhibitor that Fosun gave up before Wen Hengrui was listed is a new type of oral hypoglycemic drug that has been highly valued in recent years
.
It finds another way, by inhibiting the reabsorption of glucose by the kidneys, lowering the renal glucose threshold, thereby promoting the excretion of urine sugar, and achieving the effect of lowering the blood sugar level
.
At present, in addition to Hengrui's Henggliflozin, there are dapagliflozin, canagliflozin, empagliflozin, ipagliflozin, soxagliflozin, ipagliflozin, and topagliflozin in the world 8 drugs including Lupagliflozin were launched
.
The story of Dapagliflozin that is better known to the public is the famous scene of "soul bargaining" in the medical insurance negotiation on November 13, 2019
.
It is also due to the role of medical insurance that in the PDB sample hospital data, dapagliflozin single product has accounted for 20.
32% of the entire oral hypoglycemic drugs in Q1-Q3 in 2021
.
The story of Dapagliflozin that is better known to the public is the famous scene of "soul bargaining" in the medical insurance negotiation on November 13, 2019
.
From this point of view, in such a crowded track, it is not a wise choice for Fosun Pharma to stop losses in time, and we will wait and see how long Hengrui can recover its 270 million investment
.
Conclusion Existing drug hypoglycemic and life>
.
In October 2021, U.
S.
pharmaceutical company Vertex announced the first patient data for type 1 diabetes in the Phase 1/2 clinical trial of the research stem cell therapy product VX-880
.
On day 90 after treatment, the patient resumed his own insulin production and reduced his daily insulin injections by 91%
.
At present, hypoglycemic methods are becoming more and more diversified, and mesenchymal stem cell therapy also gives us hope of curing diabetes.
It is the core of life>
.
”