· Introduction to Erythropoietin (EPO)

Erythropoietin (EPO) is also a colony-stimulating factor, which promotes the expansion and differentiation of bone marrow erythroid colony-forming units, cooperates with other cell growth factors to promote cell proliferation and differentiation, inhibits apoptosis and increases the number of red blood cells. After the cDNA of EPO was successfully cloned in 1985, rhEPO has been widely used in the treatment of various anaemic diseases. Currently, the indications for rhEPO drugs in China are mainly for the treatment of chronic kidney disease (CKD) and chemotherapy-related anemia (CRA). It has become one of the most important supportive tools in the treatment of anaemia.

· Key indications for erythropoietin

Renal Anaemia

This is anaemia caused by relative or absolute deficiency of erythropoietin (EPO) due to various types of kidney disease, as well as anaemia caused by some toxic substances in the plasma of uremic patients by interfering with the production and metabolism of red blood cells.

Renal anaemia in China has a high prevalence, low treatment rate and low compliance rate.

High prevalence: The prevalence of anaemia in patients with CKD stages 1-5 is 22.0%, 37.0%, 45.4%, 85.1% and 98.2% respectively. The prevalence of anaemia in dialysis and non-dialysis CKD patients was 98.2% and 52.0% respectively. 

Low treatment rates: Awareness of anaemia among non-dialysis patients with CKD stages 1-5 is low, and treatment rates for anaemia are only 1 in 3. National data show that almost half of new dialysis patients have not received treatment to correct anaemia before dialysis, and anaemia is more severe in rural dialysis patients in the Midwest. 

Low compliance rate: Post-dialysis patients with renal anaemia also suffer from inadequate treatment and a low compliance rate, with the National Haemodialysis Registry reporting that the average haemoglobin compliance rate for haemodialysis patients was only 21.3% in 2011.

· Domestic recombinant erythropoietin market situation

In the past three years, the sales volume of rhEPO in domestic sample hospitals has remained stable at around RMB550 million. Domestic products accounted for over 90% of the market share, while imported products were in a weak position. There are only two imported products, Xiehe Kirin and Roche, which together accounted for 7.74% of the total in 2017. From the trend, the market share of domestic products is expected to expand the proportion. Looking at the domestic rhEPO drug market, the market competition is relatively fierce. Sansheng Pharmaceuticals alone occupies half of the rhEPO drug market, holding 53% of the market share of sample hospitals in 2017. There are 10 other domestic manufacturers, with 4 holding more than 5% share and the other 6 holding a lower market share.

· Recombinant human serum albumin: erythropoietin fusion protein

In view of the high frequency of clinical administration of similar recombinant erythropoietin drugs and the risk of toxic side effects such as abnormally high erythrocyte pressure or haemoglobin after administration, the molecular structure of our recombinant human serum albumin/erythropoietin fusion protein (rHSA/EPO) has been granted patents in China and the US. The patent discloses that the N-terminal end of the hEPO gene is fused directly to the C-terminal end of the human serum albumin gene to form a fusion protein without a no-linker between the two protein molecules, which has a longer half-life in the blood compared to rhEPO. It is expected to reduce administration frequency, reduce patient distress, and improve treatment adherence in clinical use. This could lead to better clinical outcomes and better pharmacoeconomics.

· Future development of recombinant erythropoietin drugs

According to the national tumour registry data released by the National Cancer Centre, the incidence of malignant tumours has maintained an annual increase of approximately 3.9% over the past decade or so, with approximately 3.929 million malignant tumour cases in 2015, an increase of 3.29% year-on-year. According to the Chinese Journal of Practical Internal Medicine, the prevalence of chronic kidney disease among Chinese adults is approximately 13.4%, with a high incidence. rhEPO drugs are mainly indicated for the treatment of anaemia caused by chronic kidney disease and anaemia caused by chemotherapy for oncology.  The rising incidence of tumours and the high incidence of chronic kidney disease are expected to support the continued growth of the domestic rhEPO drug market.

· The domestic market is over RMB3 billion, with Shenyang Sansheng accounting for approximately 31%, and the industry is highly concentrated.

· No long-acting EPO product is currently available in China.

· This product will be an upgrade of existing competing products in the market.

· The price is expected to be ￥800-1200/pc (production cost is ￥10/pc); sales in the first year of marketing can reach ￥50-80 million, with annual growth of not less than 30% thereafter.

· The annual production of recombinant human serum albumin/erythropoietin fusion protein injection is planned to be 3 million units, with a construction period of 4 years. The project will achieve an annual sales revenue of RMB 2 billion and an annual tax revenue of over RMB 500 million, and will arrange for the employment of more than 100 skilled workers.

· Clinical profile of recombinant erythropoietin fusion protein

Recombinant human serum albumin/erythropoietin fusion protein for injection" is a biologically innovative drug that will complete clinical phase II and aim to enter clinical phase III by the end of its third year.

The indication for this product is renal anaemic disease (dialysis patients).

Clinical phase I: 1 centre (Youan Hospital) nationwide, led by Prof. Wang Meixia; healthy subjects, 5 dose groups climbing, 1 positive control group with a total of 34 cases.

The project is now in the completion of clinical phase I and will soon start clinical phase II.

Clinical Phase II: 5 centres nationwide; 120 cases enrolled.

Clinical phase III could be initiated at the end of 3 years. (Clinical Phase 3: 15 centres nationwide; 360 cases enrolled.) .