Original research, imitation, patent litigation... pharmaceutical companies rushing to settle disputes over "weight loss miracle drugs" | weight | litigation

Large market

The Smeglutide weight loss indication was approved in the United States in 2021, but the indication has not yet been approved in China. Some consumers flock to medical institutions and e-commerce to buy drugs through informal channels, which once squeezed the medication space of patients with type 2 diabetes. Red Star Capital Bureau learned from a number of hospitals, as a prescription drug, the current supply of Simaglutide is tight.

high barriers

At present, Novo Nordisk Megraglutide is still in a patent dispute. The Smeglutide API is also facing the situation of high price, difficult mass production and high technical barriers.

Red Star Capital Bureau reported on June 11 that the Drug Evaluation Center of the State Food and Drug Administration recently updated Novo Nordisk's listing application acceptance information on the Ozempic of GLP-1 receptor agonist Simaglutide Injection. Since the drug's type 2 diabetes indication has been approved for listing in 2021, the industry generally believes that the application for listing of Simaglutide is related to the indication of weight loss.

Previously, Simaglutide was approved overseas for weight loss indications and showed good results. It is called the "weight loss medicine". The huge market demand has also exacerbated the shortage of Simaglutide.

Red Star Capital Bureau interview research found that the cost and technical barriers to high, not easy to mass production characteristics of the drug, contributed to the scarcity and popularity of drugs.

According to the API filing data disclosed by the Drug Evaluation Center of the State Food and Drug Administration, there are only 4 API filing enterprises in China, and Notai Biology, which has the largest packaging specification, is only 1 kg/bag. Notai Bio said that regarding the raw material drug of Smeglutide, the company currently has only research-use supply cooperation with some domestic head-to-head generic drug companies.

▶Concept stock fermentation/domestic pharmaceutical companies have layout.

On June 6, Novo Nordisk's new action directly led to the fermentation of the concept stock of Sime Glutide, Notai biological plate rose more than 12%, East China Medicine, Shengnuo biological and other companies also got a pull-up.

The Simaglutide weight loss indication was approved for marketing in the United States in 2021, but the indication has not yet been approved in China, and a large number of consumers flock to medical institutions and e-commerce to buy drugs through informal channels, once crowding out the medication space for patients with type 2 diabetes.

Red Star Capital Bureau learned from a number of hospitals, as a prescription drug, the current supply of Simaglutide is tight. A staff member of a public hospital pharmacy told the Red Star Capital Bureau that he needed to go to the hospital in advance to inform the doctor that the patient could take the medicine only after the doctor passed the purchase. This initiative to a certain extent to protect the use of diabetes patients.

According to Novo Nordisk's 2022 annual report, the sales of Smegllutide in China alone have reached about 2 billion yuan. The GLP-1 business income, which is dominated by Sime Glutide, is as high as about 82 billion yuan. In addition, on March 13, local time, the European Medicines Agency issued an official statement stating that selmegllutide will face a long-term shortage, which is expected to last throughout 2023, and will first be supplied to diabetic patients.

Huge market share to attract, a large number of domestic pharmaceutical companies in droves, and have to layout imitation.

According to a February research report by Guojin Securities, companies including Jiuyuan Gene, Sino-US East China, Lizhu Group, Chen 'an Biology, Federal Biology, Qilu Pharmaceutical, Shiyao Group and other companies have Simeglu peptide with indications for type 2 diabetes in research.

However, Simaglutide is still in a patent dispute, which is why domestic enterprises have not yet carried out the Simaglutide weight loss indication test.

In June 2021, East China, China and the United States filed a request with the State Intellectual Property Office for the invalidation of Novo Nordisk's Meglutide patent. In September 2022, all the above patents were ruled invalid. Novo Nordisk, whose patent period would have ended in 2026, has filed an appeal, but no results have been announced yet.

On June 10, some people in the industry told the Red Star Capital Bureau: "The progress is not so fast, and there may be a second trial."

However, due to the expiration of the patent period of the similar drug liraglutide of the previous generation of simaglutide, many domestic enterprises have gone to the final application process before listing. At present, liraglutide for the treatment of type 2 diabetes in East China, China and the United States has been approved for listing in China, while liraglutide for weight loss is in the "queue for review, china and the United States East China is expected to become the first domestic enterprises with weight-loss indications of liraglutide. In addition, Hanyu Pharmaceutical, Tonghua Dongbao, Zhengda Tianqing and other enterprises of liraglutide products are being listed in the application.

▶API expensive/a gram of thousands of dollars, the record of enterprises only 4

In addition to the uncertainty of the patent period, the high price of the raw material of Simaglutide, the difficulty of mass production and the high technical barriers are also the main reasons for the large demand but tight supply of Simaglutide in the domestic market.

According to the data of the drug evaluation center of the State Food and drug administration, up to now, only four domestic enterprises have the registration data of Simeglutide API, including Zhejiang Paipeptide Biological Co., Ltd., Hubei Jianxiang Biopharmaceutical Co., Ltd., Nuotai biological and Suzhou Tianma Pharmaceutical Group Tianji Biopharmaceutical Co., Ltd.

It is worth noting that the packaging specifications of the raw material drug of Peptin Bioseglutide are 50g/bottle, Jianxiang Bio is 200g/tin, Notai Bio is 1 kg/bag, Tianji Bio is 30g/bottle, 50g/bottle, 100g/bottle, 200g/bottle and 300g/bottle. All are small size production.

Red Star Capital Bureau learned from multiple channels that small production volume is an obvious feature of Simaglutide API, therefore, when the Red Star Capital Bureau as a buyer to Simaglutide API manufacturers inquiry, are asked what is the demand, what is the purpose. Among them, the use can determine the buyer's demand to a certain extent, for example, the demand of the research and production enterprises of the simeglutide preparation is large, and the demand of the laboratory is relatively small.

"Look at the quantity, but also look at the way of cooperation." On June 10, a salesperson of a megllutide API explained to the Red Star Capital Bureau.

Under the background of small batch production, the profit contribution of the raw material drug of Smeaglutide to domestic manufacturers is also limited. Take Notai Bio as an example, according to the Caixin News Agency, although it has Sime Glutide and Liraglutide API products, but the current revenue ratio is still small. In addition, as Smeglutide is still protected by patents, Notai Bio and some domestic head generic pharmaceutical companies only have research-based supply cooperation, but have drawn up production line expansion plans.

Depending on the demand gradient, the price of the drug substance of Smeglutide will also show different spans.

According to the Red Star Capital Bureau of different raw material enterprises, the selling price with large demand can be reduced to about 5000 yuan/g, but it is worth noting that the one-time demand is already relatively high at 1kg. For buyers who only need a few grams, they will pay a higher price. For this, some manufacturers have offered a price of 7000 yuan/g. In addition, according to a website that publicizes Sime Glutide API, the price per gram is mostly above 5000 yuan.

The Red Star Capital Bureau previously reported that Simaglutide is currently mainly divided into two dosage forms, 1.5ml or 3ml, with selling prices of 478.8 yuan/branch and 813.96 yuan/branch respectively. In the hands of scalpers, the selling price of 1.5ml specifications has been raised to 740 yuan, and the selling price of 3ml specifications is 1380 yuan.

It is reported that the high technical barriers of GLP-1 APIs are the consensus of the industry, which is safer and more effective than traditional weight loss and hypoglycemic drugs. A research report by Pacific Securities in early June mentioned that due to the complexity of peptides, the purification technology of API is very important, and the post-processing of peptides can improve the stability of drugs. Among them, the solid phase synthesis of chemical synthesis has a better ability to control impurities, but the cost is high, the purity is low, and it is not easy to mass produce.

▶Oral medicine in research/another international giant eyeing

Compared with liraglutide injected once a day and selmeglutide injected once a week, the "oral version" of weight loss drugs more popular with weight loss people may be on the market.

On May 22, Novo Nordisk released data from the Phase IIIa OASIS1 study of weight loss with selmegllutide 50mg tablets. The results showed that patients with an average baseline weight of 105.4kg who received 50mg of selmegraglutide orally lost 17.4 percent of their body weight after 68 weeks, which was statistically significant, while those who took the placebo lost only 1.8 percent of their body weight. In addition, 89.2 percent of the patients who received oral selmegllutide 50mg had lost 5 percent or more of their body weight after 68 weeks, compared with 24.5 percent of the placebo patients.

Novo Nordisk expects that the "oral version" of selmegllutide will apply for regulatory approval in the United States and the European Union within this year.

However, it is worth mentioning that another international giant Lilly is conducting research on tierpotide injection. The results of SURMOUNT-1, a phase III clinical trial of tierpotide injection, show that after 72 weeks of treatment, patients can lose up to 22.5 percent of their weight, which may be better than the "oral version" of simegllutide.

In April of this year, Lilly announced that the SURMOUNT-2 phase III clinical study of telpotide injection had achieved up to 15.7 percent weight loss in 938 adult subjects in obese or overweight patients with type 2 diabetes.

Some analysts believe that telpotide injection has the potential to compete with simegraglutide for weight loss "drug king.

The patent period of Liraglutide has passed, and the patent of Simaglutide injection has also been challenged. If the "oral version" of Simaglutide is listed before the patent period of Simaglutide, it may rebuild the wall of the weight-loss drug giant for Novo Nordisk.