On November 6, Novo Nordisk released its third-quarter report for 2024. In the first nine months of this year, sales increased by 23% to 204.7 billion Danish kroner, of which sales of diabetes and obesity treatment drugs increased by 25% to 191.8 billion Danish kroner.

The star product Semaglutide continued to advance by leaps and bounds, with sales of three brands (sugar-lowering injection Ozempic, sugar-lowering tablets Rybelsus, and weight-loss injection Wegovy) reaching 141.213 billion Danish kroner, or about 20.3 billion US dollars, in the first nine months of this year.
Not long ago, Eli Lilly also announced its performance, among which the sales of two brands of GIPR/GLP-1R dual agonist Tirzepatide (Mounjaro, a hypoglycemic injection, and Zepbound, a weight loss injection) reached US$11.0284 billion in the first three quarters of this year. Specifically, Mounjaro's sales revenue was US$8.010 billion, and Zepbound's sales revenue was US$3.018 billion.

Zepbound has been rapidly increasing in sales since it was launched in November last year, with a total of more than 600,000 patients prescribed it.

Both semaglutide and tilpotide have achieved significant sales growth this year, and the two major pharmaceutical giants are also exploring other indications of GLP-1R drugs. Perhaps new surprises are in the pipeline.

Just days ago, Novo Nordisk announced top results from Part 1 of the pivotal Phase 3 trial of ESSENCE.

The analysis showed that semaglutide (Wegovy) significantly alleviated liver fibrosis and achieved resolution of steatohepatitis in patients with metabolic dysfunction-associated steatohepatitis (MASH) compared with placebo, achieving its primary endpoint.

At Week 72, 37.0% of patients who received 2.4 mg of semaglutide had improvement in liver fibrosis without worsening of steatohepatitis, compared with 22.5% of patients who received placebo. Among patients who received 2.4 mg of semaglutide, 62.9% experienced resolution of steatohepatitis without worsening of liver fibrosis, compared with 34.1% of patients who received placebo.

Compared with other new MASH drugs, semaglutide does not perform well in improving liver fibrosis data, but this study at least proves that the GLP-1R target does have the potential to improve fibrosis, which means that GLP-1R drugs An important step has been taken in the field of treatment of MASH.

Novo Nordisk expects to submit regulatory applications for Wegovy to treat MASH to US and EU regulatory authorities in the first half of 2025. Part 2 of the trial will continue, with results expected in 2029.

The success of semaglutide and tilpotide in the preparation of a new generation of weight loss drugs has broken the deadlock of no good drugs in the obesity field for many years. However, these two drugs are not perfect, for example, they need to be administered by injection;

Demand is booming and production capacity is being challenged. And many users are troubled by its side effects, including gastrointestinal side effects such as nausea, vomiting, diarrhea, and abdominal pain, concerns about muscle loss, and rebound after drug withdrawal.

Therefore, two pharmaceutical giants, Novo Nordisk and Eli Lilly, are also developing a new generation of weight loss drugs that are more convenient, more efficient and safer.

Eli Lilly has launched the GLP-1R/GIPR/GCGR triple-target agonist Retatrutide and the oral small molecule GLP-1R agonist Orforglipron.

Retatrutide is a GLP-1R/GIPR/GCGR triple-target agonist and a potential iteration of tilpotide. The dosing frequency is once a week. Eli Lilly expects that the highest dose can reduce weight by 22-24%, mainly fat reduction, and the hypoglycemic effect is expected to reduce Hb1Ac by 2%.

Currently, Eli Lilly has registered 9 phase III clinical trials around Retatrutide: 3 for type 2 diabetes and 6 for weight loss, including a head-to-head study of tilpotide for weight loss with Retatrutide. The study plans to enroll 800 obese patients and is expected to be completed in April 2027.

Orforglipron is a new oral small molecule GLP-1R agonist administered once daily. Currently, the drug is in clinical phase III, and its indications include obesity, type 2 diabetes, and cardiovascular disease.

Phase II clinical data of Orforglipron showed that after 36 weeks of treatment, the 45 mg dose group lost 14.7% of their weight, compared with 12.4% of the placebo group.

Compared with the 14% weight loss in the 36-week OASIS 1 clinical trial of the oral Semaglutide 50mg group, orforglipron seems to have a better weight loss effect. As the leader in the GLP-1R small molecule track, orforglipron's performance has made people full of expectations for its Phase III clinical data.

Novo Nordisk has launched CagriSema, a drug combination of Semaglutide and the amylin analog cagrilintide, as well as oral drugs monlunabant and amycretin.

CagriSema is a fixed-dose combination of semaglutide and the amylin analog cagrilintide, administered by subcutaneous injection once a week.

In 2022, Novo Nordisk began the Phase III clinical series REDEFINE of CagriSema obesity, including a Phase III clinical trial (REDEFINE 4) of CagriSema versus telpotide head-to-head for weight loss. The study plans to enroll 800 obese or overweight patients to receive 2.4mg Cagrilintide + 2.4mg semaglutide or a high dose of telpotide 15mg, and is expected to be completed in August 2025.

Monlunabant (formerly known as INV-202) is a small molecule oral cannabinoid receptor 1 (CB1) inverse agonist. Novo Nordisk acquired this therapy in August 2023 by acquiring the Canadian company Inversago pharma for more than $1 billion.

The results of its Phase 2a clinical trial showed that starting from a baseline weight of 110.1 kg, after 16 weeks of treatment, participants who took a 10 mg dose of monlunabant once a day lost an average of 7.1 kg, while the placebo group only lost 0.7 kg. However, the weight loss effect seen in the high-dose group of monlunabant was limited.

Amycretin is a long-acting co-agonist of the GLP-1 receptor and amylin receptor. Novo Nordisk has developed two dosage forms, oral and subcutaneous. The oral dosage form has faster clinical progress and is administered once a day.

In terms of weight loss, after 12 weeks of treatment, the weight loss of patients in the Amycretin group reached 13.1%, compared with only 1.1% in the placebo group.

In the emerging field of weight loss and metabolism, domestic innovative drugs also occupy an important position.

In November 2023, Chinese biotech company Chengyi Bio and AstraZeneca reached an exclusive licensing agreement of more than US$2 billion for the small molecule GLP-1R agonist ECC-5004.

In May 2024, Chinese pharmaceutical giant Jiangsu Hengrui Medicine licensed the rights of its GLP-1R drug portfolio outside China to the newly established US biotechnology company Hercules. The total transaction amount exceeded US$6 billion, and the newco model opened up by this is becoming a new trend for innovative drugs to go overseas.

With the advancement of the research and development of domestic GLP-1R drugs, it is expected to achieve breakthrough progress in this new field and get a share of the pie.

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