· Brief Introduction of Granulocyte Stimulating Factor ( G-CSF )

Clinical application of granulocyte stimulating factor

1. To promote the increase of neutrophil number during bone marrow transplantation.

2. Prevention of neutropenia caused by anti-tumor chemotherapy drugs and shortening the duration of 

neutropenia; Solid Tumor; Acute Lymphoblastic Leukemia. 

3. Neutropenia in myelodysplastic syndromes.

4. Neutropenia in aplastic anemia.

5. Congenital and primary neutropenia.

6. Secondary neutropenia to immunosuppressive therapy (Kidney transplat).

· Main indications of granulocyte stimulating factor

Neutropenia

Neutrophils are chemotactic, phagocytic and bactericidal. The main complication of neutropenia is infection, which is the main cause of death from chemotherapy.

Absolute neutrophil count (ANC) <0.5X10(9) or expected to decline from <1.0X10(9) to <0.5X10(9)

Degree of neutropenia

· Market situation of granulocyte stimulating factor drugs

Granulocyte stimulating factor drugs

Currently, there are two types of granulocyte-stimulating factor drugs on the market: short-acting and long-acting. The short-acting drug’s generic name is filgrastim. It was jointly developed by Amgen and Kyawa Hakko Kirin, and was approved by the FDA and PMDA, be on market in the US and Japan respectively in 1991.

In 2002, Amgen launched the world's0 first long-acting granulocyte-stimulating factor drug, PEG-rhG-CSF, commonly known as pegfilgrastim, and the PDB database shows that Amgen's sales of granulocyte-stimulating factor drugs (long-acting + short-acting) have stabilised in recent years at around US$5.5 billion.

· Granulocyte stimulating factor: long-acting drugs dominate the market

Amgen's granulocyte stimulating factor dominates the global market for this drug and almost monopolize the long-term dosage form market.

At the same time, according to the global top 500 database in PDB, in the long-acting and short-acting dosage form sales structure of this drug of Amgen, long-acting dosage form (pefegstine) is the leading sales dosage form, and the proportion of long-acting dosage forms is still increasing. In 2017, Amgen had $549 million in filgrastim sales, $4.798 billion in pegfilgrastim, long-acting sales is of about ten times the short-acting dosage form.

· Granulocyte stimulating factor： domestic market

In recent years, sales of granulocyte-stimulating factor (rhG-CSF) in sample hospitals have continued to grow, accelerated by the release of long-acting dosage forms. rhG-CSF (including short-acting and long-acting) sales in sample hospitals were RMB1.277 billion in 2017, up 27.91% year-on-year. rhG-CSF sales increased significantly mainly due to the release of long-acting rhG-CSF. In 2017, long-term rhG-CSF sales were 449 million yuan, up 256.08% year on year, up to 35%.In the past three years, the short-acting market has remained stable,.From the long-term trend, the long-acting will gradually form an alternative effect on short- acting drugs.

· Granulocyte stimulating factor： domestic market competition

At present, the domestic short-acting rhG-CSF market competition is fierce, with nearly 20 companies listed and marketed, the top five companies together accounting for 75% of the total. Among them, Qilu Pharmaceutical is the leader, maintaining a share of over 40% in short-acting formulations each year, while the remaining companies, Xiehe Fermentation, Tebao Bio and Jiuyuan Gen, maintain a share of around 6-10% each year. At present, only Qilu Pharmaceutical and Shiyao Group produce and sell long-acting rhG-CSF in China, and both companies have maintained high growth in recent years.

· Future development of long-acting granulocyte stimulating factor drugs

Overall, the long-acting rhG-CSF market has a good competitive landscape. Domestic long-term dosage form only Qilu pharmaceutical and Shiyao Group listed sales. Hengrui's thiopegfilgrastim was marketed in 2018 and negotiated a price reduction into medical insurance in 2019, with the latest tender price of RMB3,080 in January 2020 , lowest cost in the three long-acting G-CSF products. Lower cost is expected to bring about an increase in drug penetration rate in patients.

The new increase of  cancer patients in China is about 4.5 million every year. Chemotherapy is the treatment of choice for most cancers and the end line treatment when no other drugs are available, so most cancer patients will use chemotherapy once or more. According to an article published by CNKI, chemotherapy is used in 57%, 14% and 72% of patients with non-small cell lung cancer, cervical cancer and stage 3 rectal cancer respectively.

The 2019 NCCN guidelines indicated that the rate of neutropenia in patients with initial chemotherapy was up to 25% to 40%. Assuming that 50% of people use chemotherapy and 30% of them require the use of leucovorin, the number of patients corresponding to leucovorin per year is 450*50%*30% = 675,000. On average, each person is treated with chemotherapy 5 times, then 5 times of long-acting leucovorin is needed, and the amount of each dose is about 3000 RMB. The market space for domestic long-acting chemotherapy drugs is calculated to be 67.5*5*0.3=10.1 billion RMB. Compared to the current 3.6 billion RMB, the penetration rate is now only 36% and there is still room for doubling.