Liraglutide patents expire, and generic drug research and development go hand in hand

In 2021, Novo Nordisk generated sales of DKK 140.

Novo Nordisk share of the global diabetes market (Source: Novo Nordisk 2021 Public Financial Report)

Founded in 1923, Novo Nordisk Corporation is a leading global biopharmaceutical company headquartered in Denmark

Table 1 Novo Nordisk 2021 annual financial report

Source: Novo Nordisk 2021 Public Financial Report

GLP-1, or glucagon-like peptide-1, is an intestinolin-secreting hormone

Since the launch of the first GLP-1 analogue from lizards (Byetta) in 2005, nearly 10 GLP-1 agonist hypoglycemic drugs have been approved worldwide (Table 2), including exenatide, liraglutide, abiraglutide, dullaglutide and someric glutide

Source: FDA official website| Tabulation: Biodiscovery Editorial Team

Among them, Victoza® is a daily injection, which was listed in the European Union in 2009 and in China in 2011 (trade name "Novoli") (Figure 2).

In fiscal 2021, Ozempic's® sales increased 59% in Danish krone terms and 64% at fixed exchange rates to DKK 33,705 million (approximately USD 5,147 million); Rybelsus® sales increased by 158% in DKK and 168% in fixed exchange rate terms to reach DKK 4,838 million (USD 739 million).

In the field of weight loss, Novo Nordisk's GLP-1 products include Saxenda® (liraglutide injection) and Wegovy® (weekly preparation of smeglutide injection, 2.
4 mg size).

These two products contributed DKK 8.
4 billion (USD 1.
283 billion) in revenue in 2021, up 50%
year-on-year.
For example, in the field of weight loss, the above two GLP-1 drugs in the field of weight loss will contribute a total of $9.
5 billion in revenue in 2021, nearly $10 billion
.

Liraglutide occupies an absolute monopoly position in China's GLP-1 market

In the Chinese market, Novo Nordisk generated sales of DKK 16,019 million (USD 2.
4 billion) in 2021, up 14% in Danish krone terms and 11%
at fixed exchange rates.
The Chinese market accounts for 11% of the global market share (Figure 3), and the steady growth of performance is mainly due to the rapid release of
GLP-1 liraglutide after entering the national medical insurance.

Novo Nordisk global regional market share (Source: Novo Nordisk 2021 public financial report)

Liraglutide (Victoza®) in 2011 with the trade name "Novoli ®" listed in China, but the high price of the original drug makes the market size is not large, until 2017 into the national medical insurance directory, the price dropped from 723 yuan / stick to 410 yuan / stick, after which the rapid release of liraglutide, 2019, 2020, 2021 Liraglutide in China performance of 8.
98, 10.
33, 1.
544 billion Danish crown
.
Sales in 2021 were approximately RMB1.
494 billion, up 45%
year-on-year.

According to the statistics of Southwest Securities Research Report, the sales of liraglutide PBD in 2019 reached 220 million yuan, accounting for 92%
of China's GLP-1 market share.
In 2021, with a sales performance of 1.
494 billion yuan, liraglutide occupies an absolute monopoly position in
China's GLP-1 market.

However, at present, GLP-1 receptor agonists are still in the small category in China and are still in the market cultivation period
.
Since 2015, the proportion of sales of GLP-1 receptor agonists has shown a slow upward trend, and the domestic GLP-1 receptor agonist market size in 2019 was 1.
1 billion yuan, accounting for about 3%, and traditional oral drugs such as insulin and biguanides, sulfonylureas and α-glycosidase inhibitors still account for a large proportion
.
The foreign GLP-1 market share has rapidly increased to 19%, and there is still a lot of room for improvement and market potential in China (Figure 4
).

The proportion of major drugs in China's diabetes market (Source: Southwest Securities Research and Development Center)

Somaglutide is listed in China and quickly enters medical insurance

On April 27, 2021, China's State Drug Administration (NMPA) approved the marketing of Novo Nordisk's ® Semaglutide (Semaglutide injection, commonly known as somaloglutide) for weekly subcutaneous injections to aid diet and exercise to improve blood sugar control
in patients with type II diabetes mellitus (T2DM).
Novotec ® is the second GLP-1 new drug product listed in China after Novo Solid, and ® the eighth GLP-1 receptor agonist-related drug in the
domestic market.

On December 3, 2021, according to the latest announcement of the National Medical Security Bureau, Novo Nortec ® (Simeglutide Injection) was included in the National Basic Medical Insurance, Industrial Injury Insurance and Maternity Insurance Drug Catalogue (2021).

The data of Yaorong Cloud (www.
pharnexcloud.
com) shows that the price of Simeglutide injection before entering medical insurance: 1.
5 ml/stick and 3 ml/stick, which are 1120 yuan / stick; 1904 yuan / stick
.
After the price reduction, the price of 3 ml/stick is: 814 yuan / stick, and the price reduction is more than 57%.

The price of 1.
5 ml/stick is 479 yuan
.

As China's first and currently the only GLP-1RA weekly preparation for adult type 2I diabetic patients with cardiovascular indications, Novo Thai ® has a half-life of up to 7 days, achieving once-a-week administration, safe and powerful sugar control, "on-demand" accurate compliance, and comprehensive cardiovascular and metabolic benefits
.
Novotec's ® inclusion in the medical insurance directory reimbursement system will enable more Chinese type II diabetics to benefit from this effective, simple and safe treatment plan
.

Sommarutide entered the new health insurance catalogue very quickly, just 7 months
after the product was first approved in the Chinese market.
In the first year of its listing in 2021, Novostec's ® China (covering Hong Kong, Macau, Taiwan and other regions) reached DKK
303 million.

Liraglutide patents expire, and generic drug research and development go hand in hand

Since the crystal patent of the original research of liraglutide expires in 2020 (Table 3), more than 10 enterprises have carried out the imitation of liraglutide injections in China, including Hanyu Pharmaceutical, Tonghua Dongbao, Jiangsu Wanbang (under Fosun Pharma), Federal Pharmaceutical, Dongguang Medicine, Runzhong Pharmaceutical and Jiuyuan Gene (under East China Pharmaceutical).

Among them, 7 companies are undergoing phase III clinical trials, and 5 companies are initiating Phase I clinical BE trials
.

Table 3 Patent status of Novo Nordisk in key markets

Source: Novo Nordisk 2021 Public Financial Report

At present, the fastest progress is East China Medicine, in September 2021, the CDE official website shows that East China Pharmaceutical Liraglutide Injection Diabetes Indications application has been accepted, in accordance with the relevant drug registration regulations, is expected to be approved for listing
in 2022.
It is understood that this is the first domestic liraglutide biosimilar to be produced
.
Once a generic drug is approved for listing in China, the price will impact the original drug
.

The patent expiry date of Somaglutide in China is 2026
.
Tonghua Toho has laid out somaglutide in advance, taking the lead in preclinical research, and is expected to achieve rapid listing
when the patent expires.
Since the launch of oral somaglutide in 2019, the world has also set off a wave
of oral GLP-1 receptor agonist research.
At present, only the oral preparation new drugs of Hengrui and Huadong Pharmaceutical in China have entered the clinical stage
.

As the most ideal hypoglycemic drug at present, GLP-1 receptor agonists can effectively reduce blood sugar, and liraglutide and somaglutide have also been shown to have cardiovascular benefits
.
Although the current market share of GLP-1 in China is only 3% due to the high price and low patient awareness, as GLP-1 is gradually included in medical insurance to reduce costs, and GLP-1 is recommended by the consensus document issued by the latest diabetes association in 2020, while domestic generic drugs and new drugs have been launched, it is bound to promote the rapid increase
in the market share of GLP-1 drugs in China in the future.