From the long-term insulin Icodec phase III study Grand Slam, looking at the development history of Novo Nordisk

Recently, Novo Nordisk announced its insulin icodec 1 times a week in a ONWARDS 5 stage IIIa clinical trials for top line positive results. Data show that patients with type 2 diabetes who received once-weekly icodec insulin had greater reductions in glycosylated hemoglobin (HbA1c) levels than those who received once-daily basal insulin. Novo Nordisk expects to file a marketing application for icodec insulin in the United States, Europe and China in the first half of 2023.

Icodec is a long-acting basal insulin analog developed by Novo Nordisk researchers by modifying insulin molecules. The molecule reduces its affinity for insulin receptors while introducing fatty acyl modification, resulting in a half-life of up to 196 hours. After injection, icodec binds tightly and reversibly to albumin, creating a "circulating reservoir" that provides a continuous and steady release of insulin to meet the patient's baseline insulin needs for a full week.

Participants in the ONWARDS 5 study included 1,085 people with type 2 diabetes who had previously been treated without insulin. The efficacy and safety of weekly injections of icodec insulin were compared to daily injections of basal insulin in a 52-week trial.

The results showed that at 52 weeks, icodec insulin treatment reduced HbA1c levels by 1.68% compared with 1.31% in the once-daily basal insulin group (a difference in response of approximately 0.38% between the two groups), meeting the primary end point. CODEC-insulin demonstrated excellent safety and tolerability in the trial and no significant difference in the frequency of hypoglycemia was found between the two treatment regimens.

Earlier, with the exception of the five ONWARDS studies, the remaining studies have been readout this year and have achieved their primary endpoints. This confirms the potential of once-weekly insulin icodec.

There are currently no approved marketing-ready products for weekly insulin in the world, and Novo Nordisk is leading the way. In fact, Novo Nordisk, the world leader in the treatment of diabetes, was born and raised on insulin. The birth and development history of Novo Nordisk is closely related to the evolutionary history of insulin. We take this opportunity to review the history of the century-old giant Novo Nordisk.

Based on the discovery of insulin, Novo Nordisk and Novo LABS were founded.

Until 1921, diabetes was a terrible killer of humans. Once you have diabetes, you can only survive on extreme diets. In July 1921, Banting, a Canadian physician, successfully extracted the substance from the pancreas of dogs, which could lower blood sugar in diabetic dogs. Insulin was not officially invented until then. Banting and another scientist, MacLeod, won the 1923 Nobel Prize in Physiology or Medicine for their work.

When Banting's discovery of insulin shocked the world, fellow Nobel laureate Professor Kroeger, of the University of Copenhagen in Denmark, and his wife were on holiday in the United States. His wife, Mary, is a doctor and diabetic. With professional sensitivity, they recognized the value of insulin to their patients and sought a license to produce it in Denmark, which they negotiated.

Back in Denmark, the Krogs founded Nordisk Laboratories, a company specialising in large-scale industrial production of insulin, the forerunner of today's Novo Nordisk..In late 1923, Nordisk Laboratories first produced Insulin Leo in small amounts from the pancreas of cattle and marketed the product under the name Insulin Leo..To achieve mass production, they hired Harald Pedersen, the brother of the engineer, who was responsible for the design and manufacture of the production equipment, as well as the chemical processes and quality analysis.

Soon after, the Pedersen brothers left the company to start their own business. They formed Novo LABS with the intention of producing their own insulin, and in 1925 Novo Laboratories introduced its first product, Insulin Novo. The Pedersen brothers subsequently formed the company and named it Novo Therapeutisk.

The two companies chased each other, and the insulin industry grew rapidly.

Nordisk and Novo went back and forth in the decades that followed, with Novo introducing the first zinc-based insulin in 1937 and a premixed version in 1944 that was well received by the harvest market..Nor is Nordisk, which made prasugrel insulin crystals in 1946, sitting idle..The significance of this was that the pre-mixed prasugrel did not need to be re-mixed, and patients could inject it with a slight shake..In 1950, Nordisk's premixed propranolol insulin was approved for sale in the U.S. Novo subsequently introduced a new product, Novo Lente, which had a lower allergy rate than premixed propranolol and was a best-seller in the 1950s and 1960s.

After the introduction of premixed insulin in the early 1970s, both sides began to develop highly purified insulin. Later, Novo discovered that the sequence of insulin in humans and pigs differed only by an amino acid, so it began replacing that amino acid with a chemical reaction, initiating the first chemical transformation of insulin in 1982. Novo then delved into the field of genetic recombination, and in 1987 launched the company's first recombinant human insulin. Nordisk also pioneered the field of genetic recombination techniques, introducing Norditropin, a recombinant human growth hormone, in 1985.

Eventually, Novo went public in 1974 and Nordisk in 1986. At the time, however, both companies were the world's largest producers of insulin.

Strong nations unite for a better future.

Entering the 1980s, mergers and acquisitions of strong companies in the face of a complex international competitive environment became a major trend in the pharmaceutical industry, and in 1989 Novo merged with Nordisk to become Novo Nordisk, with Novo CEO Mads Ovlisen as CEO of the new company.

Novo Nordisk then launched the NovoLet, the world's first pre-filled insulin injection pen, and expanded overseas..In the mid-to-late 1990s, Novo Nordisk partnered with Boehringer Ingelheim and Schering-Plough to jointly launch the oral anti-diabetic drug Novonorm / Prandin..At the same time, Novo Nordisk has stepped up research and development of its third-generation insulin..In 1999, its first third-generation insulin, NovoLog (insulin aspart), was approved for sale, which broke Eli Lilly's dominant position in the U.S. insulin market at that time. In addition, Novo Nordisk also has a central nervous system (CNS) segment. Novo Nordisk's first CNS drug, Seroxat (paroxetine), was approved for antidepressant treatment in 1992. In 1995, its innovative antiepileptic drug Gabitril (tiagabine) was approved for marketing, and the research and development efficiency is particularly high.

Profoundly focused on the diabetes field, as much as possible to achieve the best possible product.

After 2000, Novo Nordisk became more focused on diabetes and quickly captured most of the market for fast-acting insulin, but insulin glargine, a third-generation extended-acting insulin from rival Aventis, quickly gained market share. For this reason, Novo Nordisk also launched the world's first fatty acid-related insulin, insulin-DET, in 2004 and won some market share.

In the GLP-1 space, Novo Nordisk launched the company's first GLP-1 analog, Liraglutide, in 2009. It was also the world's first human-derived GLP-1, which quickly won market acceptance and generated significant cash flow for Novo Nordisk. Then Novo Nordisk introduced Degu insulin, Somarlutide and others.

As a global leader in anti-diabetic drugs, Novo Nordisk focuses almost exclusively on the research and development, fine-tuning and ongoing optimization of anti-diabetic drugs. At present, Novo Nordisk has a rich variety of antidiabetic drug products (long-acting insulin, premix insulin, rapid-acting insulin and additional insulin and GLP-1 antidiabetic drugs), and its antidiabetic drug sales account for a significant proportion in the antidiabetic drug market of major countries in the world. Evaluate Pharma expects its global market share to climb to 35.5 percent by 2024. Icodec, which recently achieved a grand slam of Phase III studies, will revolutionize insulin once it hits the market.

Novo Nordisk has been in business for approximately 100 years and has been actively exploring the treatment of diabetes. Its focus and emphasis on user experience has resulted in the introduction of a wide range of convenient and easy-to-use products that have considerably increased the market competitiveness of its products. Novo Nordisk's adherence to insulin has played an irreplaceable role in the evolution of insulin over the past 100 years.