Can oral insulin rewrite the 100 year game outcome of diabetes giants?

As one of the oldest biological drugs, insulin is the first recombinant protein drug, which has milestone significance for human health and new drug developmentThe history of insulin is also a good storyThere are the coincidences between the stubbornness of individual characters and fate, the rise and separation of key companies, commercial greed and game, but innovation has no end< br / > at present, more than 80% of the global insulin market with a market value of US $23 billion is third-generation insulin, with weekly insulin intake and oral insulin as new hot spotsAt present, oral insulin R & D company has established a cooperative relationship with Chinese biotechnology enterprisesOnce the product is launched, Chinese diabetes patients will take the lead in using new drugs< br / > oral insulin has gone through many twists and turns from conception to clinical practiceOn the one hand, a few companies have published positive results, on the other hand, more diabetes companies have made arduous research and developmentIn addition, the United States, as a global medical center and wind vane, has been trapped in the dilemma of rising insulin prices year by year, even requiring administrative pressure to intervene; and in the first quarter of 2019, the advent of several new insulin technologies finally showed a glimmer of progress< br / > especially in March 2019, Novo Nordisk, a biopharmaceutical company that once suffered from oral insulin R & D Waterloo, rallied and submitted an application to FDA for approval of the oral drug semaglutide to reduce the risk of major cardiovascular events (MACE) in patients with type 2 diabetes< br / > in addition, the trend of Chinese diabetes market is also remarkableDue to different treatment levels and market access, the domestic diabetes drug market is quite different from the global market: in medical institutions, all kinds of drugs are equally divided; in the retail end, oral hypoglycemic drugs account for the main market shareIn the first quarter of the outbreak of new insulin technology in 2019, some companies aimed at the Chinese market, hoping to "borrow" domestic enterprises to enter the new market< br / > to this end, the arterial network reviewed the magnificent history of insulin and the latest progressAnd a good story starts with the key characters< br / > the birth of two Nobel laureates and the rise of two giants < br / > in 1869, German pathologist Paul Langerhans (1847-1888) discovered the islet of Langerhans, which was named "isles of Langerhans"; at that time, Langerhans thought it was a kind of divine cellIn 1910, British physiologist Edward Albert Sharpey Schafer (1850-1935) proposed that diabetes was caused by the lack of a substance secreted by the pancreas under normal conditions He named this substance insula < br / > it wasn't until 1917 that Frederick Banting, who had returned from World War I, opened a clinic for a living and worked in a medical school to subsidize his family In 1920, Banting saw a case report when preparing for class He found that a patient's pancreatic duct was blocked by stones, and the digestive gland secreting digestive enzymes shrank, but the islet cells still survived well Banting was greatly inspired: if the animal's catheter was surgically ligated, the active insulin could be extracted from the digestive gland < br / > at this time, Banting was full of ambition and resolutely resigned from all work and went back to his alma mater, the University of Toronto, for the help of Professor mclaide, an authority on diabetes Mcclaird didn't take the idea seriously, but gave in to Banting's persistence < br / > in the end, Banting applied to a laboratory and 10 dogs as experimental materials The college also sent Charles best, a young assistant to him < br / > before insulin was found, diabetes was a widespread and death threatening disease Patients had no choice but to take starvation therapy, but the effect was unknown At the same time, many scientists tried to extract insulin from the pancreas, but failed, because insulin will be destroyed by digestive enzymes as the pancreas is destroyed < br / > but Banting and best's experiments turned around at this time, and a dog used for the experiment returned to normal blood glucose after insulin injection Next, the two bought back the bovine pancreas for repeated experiments, and directly treated with acidified alcohol to destroy the digestive enzymes of the pancreas to prevent insulin degradation Even the two injected themselves with bovine insulin to prove their safety < br / > then, one of Banting's classmates, Liszt, came to the door for help because of the deterioration of diabetes Banting and best injected him with bovine insulin Liszt's condition soon improved - the experiment was finally successful, but the insulin prepared by the two men had been used up As it happened, it reached mcclaird, who realized the importance of the matter and began to mobilize all resources to promote insulin research Banting and best are not alone Krip, a biochemist at the University of Toronto laboratory, further purified bovine insulin < br / > it is worth mentioning that several scientists applied for patents and transferred them to the University of Toronto at a symbolic price of US $1 per person At the same time, in order to promote their application, they also authorized the patents to Lilly and Novo Nordisk enterprises for commercial production < br / > insulin has gone from laboratory to commercial market < br / > when Lilly launched its first commercialized insulin in 1923, Novo Nordisk, which later became a famous pharmaceutical giant, is still in its infancy < br / > in 1922, August Krogh, the Nobel Laureate in physiology and medicine, and Marie Krogh, the wife of doctor of medicine, were invited to visit Yale University They just heard about Banting and best's report on the treatment of diabetes with bovine pancreatic extract Marie Krogh is very interested because she is a type 2 diabetic The two then wrote to mcclaird hoping to have a discussion After the authorization agreement for the production and sale of pancreatic extracts in northern Europe was reached, the couple established Nordisk insulin laboratory in cooperation with Dr Hans Christian Hagedorn In the spring of 1923, the first diabetic was injected with insulin produced in these laboratories Later, Nord insulin laboratory began to market the insulin product, which was also considered as the founding year of Nord < br / > at the beginning of its establishment, Nord faced the first problem: who would be in charge of the manufacturing of insulin production equipment In 1924, Harald Pedersen, a mechanic who joined Nord and had a talent for rare inventions, became the first choice < br / > it's surprising that Harald Pedersen and Hans Christian Hagedorn can't come together and quit in a rage By the way, he took his brother, thorvald Pedersen, a pharmacist Thorvald Pedersen was previously in charge of the analysis of chemical preparation processes related to insulin production in Nord The two brothers began to develop their own insulin, and in 1924, they prepared a stable liquid insulin preparation Harald Pedersen invented the novo syringe, the insulin syringe that is still in use today < br / > at first, the Pedersen brothers wanted to go back and work with Nord to bring their insulin products to market Nord refused to forgive the two defectors So the two brothers started their own business and named the company novo terapeutisk Laboratorium They sold insulin and novo needles developed by Novo, which surpassed Nord in one fell swoop < br / > since then, the two insulin companies have been competing for decades Nord has made continuous breakthroughs in new product development In 1936, Hans Christian Hagedorn and Norman Jensen found that protamine can delay the release of insulin Neutral protamine insulin was listed in 1946 and named after Hans Christian Hagedorn: neutral protamine Hagedorn, NPH for short < br / > Hans Christian Hagedorn failed to surpass the old rivals as expected, and Nord's overall market performance was better than that of Nord By 1989, if we ranked the world's insulin manufacturers, Nord was in third place, and Nord was in second place < br / > at this time, insulin got rid of the animal insulin stage and entered the gene recombinant human insulin stage in the game between technology and market of major companies The struggle of the major giants has also become intense < br / > at last, a dramatic turn has taken place For strategic reasons, the two companies finally "shake hands" and form a new company, Novo Nordisk The world's largest insulin producer was born, and this market pattern continues to this day < br / > new century, new turning point < br / > Novo Nordisk has not stopped its development after entering the 21st century At this time, the sales growth of recombinant human insulin gradually stagnated, and the market share decreased from 90% in 2000 to 14% in 2015 Novo Nordisk needs to try to innovate the form of insulin administration and meet the challenges brought by the advent of new insulin delivery technology and diabetes giants from other regions of the world < br / > in fact, since insulin was commercially available, the form of injectable administration has dominated the insulin market In 1924, the second year of the birth of Nord laboratories, the concept of oral insulin appeared in professional papers due to the inconvenience of injection behavior and skin pain However, even if the scientific community continues to overcome the technical difficulties, until now, the global diabetes patients have to face the inconvenience of drug administration and the fear of injection in addition to the war with the disease itself < br / > this situation will change in the 21st century < br / > in 2006, the biomedical company oramed pharmaceuticals (NASDAQ: ORMP) was established in the medical center of hadassa University in Jerusalem, Israel, and attracted much attention due to its breakthrough in oral insulin technology In 2015, oramed pharmaceuticals and Hefei Tianhui incubation Technology Co., Ltd (htit) reached a strategic cooperation and obtained US $50 million investment to support the development of the company's revolutionary flagship product, oral insulin capsule (ormd-0801), which completed the clinical phase IIB experiment in that year < br / > but in 2016, Novo Nordisk suddenly announced the cancellation of its development plan for oral insulin candidate i338, despite the success of phase II trials of this insulin tablet The industry still speculates that Novo Nordisk has to give up its R & D plan due to the high threshold of drug production and tight financial budget In the same year, the insulin pen developed by Novo Nordisk has become the mainstream instead of insulin pump < br / > according to statistics, most insulin users, about 70% to 93% (different due to the data used and the research area), are using insulin pens, thus eliminating the cumbersome process of using syringes to extract insulin from insulin vials < br / > oral insulin is a step away from the market because of the withdrawal of Novo Nordisk At this time, only two companies in the world continue to work in this field In addition to oramed pharmaceuticals, there are also some biomedicals in Ohio, USA < br / > hdv-i, the company's oral insulin, uses liver cells to target liposomes to deliver insulin to the liver, and achieves the goal of reducing blood sugar by promoting the absorption of glucose by the liver Hdv-i is currently undergoing phase III clinical trials < br / > a new round of turning machine appears again By 2019, the once silent oral insulin technology had exploded in the first quarter < br / > on February 13, 2019, according to the balance principle of cheetah tortoise, MIT cleverly designed a new oral insulin device by using bionics < br / > in March, Rani therapeutics, based in San Jose, California, announced the completion of the first human trial of its robotic capsule ranipill, which is designed to provide a note from the digestive tract