Growth hormone deficiency, known as dwarfism, is caused by the dysfunction of growth hormone secretion in the pituitary gland. Growth hormone deficiency can affect the physical development of children, such as being shorter and lighter than children of the same age. Untreated children with growth hormone deficiency have impaired growth and development, increased fat content, decreased muscle mass, and decreased bone density, and led to an increased risk of cardiovascular disease.
According to data from the Chinese Medical Association, there are currently nearly 40 million children with short stature in China, and the stock is huge. There are about 7 million children aged 4-15 who need treatment, but the current number of patients treated each year is less than 300,000. There are less than 30,000 patients actually receiving treatment, and the penetration rate of drug therapy is less than 1%. Compared with the penetration rate of more than 10% in developed countries in Europe and America, there is huge room for improvement. Recombinant human growth hormone has huge potential in the domestic market.
The annual cost of long-acting growth hormone is nearly 200,000
At present, the commonly used drugs for children with growth hormone deficiency are recombinant human growth hormone, including powder injection, water injection and long-acting dosage forms. The specific treatment plan for short-acting growth hormone is: 6-7 growth hormone replacement therapy per week The subcutaneous injection dose is 22-35μg/kg/d (0.16-0.24mg/kg/week) or intravenous injection at a dose of 12IU (4mg) per square meter of body surface area per week until the epiphyseal line is closed. The recommended dosage of long-acting growth hormone is 0.2mg/kg/time, administered by subcutaneous injection once a week. According to the drug bidding information, the annual cost of auxin powder injection is nearly 19,000 yuan, the annual cost of water injection is about 42,000 yuan, and the annual cost of long-acting dosage forms is about 196,000 yuan.
Children are the main treatment targets of recombinant human growth hormone, and the daily injection of the above-mentioned treatment plan is likely to cause physical discomfort and psychological fear in children, which will lead to rejection of treatment and relatively poor treatment compliance. Another study has shown that skipping 1-2 injections a week will significantly reduce the therapeutic effect. Therefore, there is an urgent need for the development of long-acting growth hormone in the market. Long-acting growth hormone has the same therapeutic effect as short-acting growth hormone. It will reduce the frequency of injections and patient compliance will be higher.
At present, the only long-acting growth hormone preparation on the market in China is the polyethylene glycol recombinant human growth hormone injection of Jinsai Pharmaceuticals approved in 2014. According to public data, the current sales of this long-acting preparation account for about the entire growth rate. 11% of the hormone market, but because of its high unit price, the current sales of long-acting preparations are not high.
$6 billion! The scale of the global childhood growth hormone deficiency treatment market in 2030
According to data from Frost&Sullivan (as shown in the figure below), from 2018 to 2030, the global market for the treatment of growth hormone deficiency in children will increase at a compound annual growth rate of 6.4%. It is expected that the treatment of growth hormone deficiency in children will be global by 2030 The market size will reach 6 billion US dollars. In addition, the market size for the treatment of growth hormone deficiency in children in China has increased at a compound annual growth rate of 33.5% from 2014 to 2018. The market size in China is expected to increase by 15.7% from 2018 to 2030. The market size of treatment will also reach 3.2 billion US dollars, or about 22.136 billion yuan.
11 long-acting growth hormone drugs are under development, 2 have been submitted for marketing applications
At present, the main global R&D trend of growth hormone is long-acting growth hormone. The long-acting growth hormones that have been approved for the market and are still on the market include the polyethylene developed by Jinsai Pharmaceuticals approved in China in 2014. Glycol recombinant human growth hormone injection and Somapacitan developed by Novo Nordisk, which was approved in the United States in September 2020.
Somapacitan uses growth hormone albumin binding technology to form a non-covalent bond between terminal fatty acids and albumin through unit point mutations on the recombinant human growth hormone skeleton. This modification method can reduce renal excretion and extend the half-life in the body , Thus forming a long-acting dosage form of growth hormone.
According to Yaozhi data, Somapacitan has obtained an implicit license for clinical trials in China. The polyethylene glycol recombinant human growth hormone injection developed by Jinsai Pharmaceutical is a covalent conjugate composed of recombinant human growth hormone and branched PEG. The recombinant human growth hormone used is secreted by genetically recombinant Escherichia coli Technical production, and then modified and formed by PEG, can prolong its half-life in human blood, reduce the frequency of injections, improve patient compliance, and improve the therapeutic effect.
Currently, there are 11 long-acting growth hormone drugs in clinical research in the world, of which 2 have been submitted for marketing; 2 projects have been completed in phase III; 2 projects are still in clinical phase III, and the rest The clinical status is shown in the table below.
Somavaratan (VRS-317), Somatrogon (MOD-4023), and ACP-011 use protein fusion/conjugation technology. VRS-317 is a recombinant human growth hormone fusion protein developed by Versartis Inc. The drug uses a proprietary half-life extension technology called XTEN, which is licensed for use by AmunixOperating, Inc. This technology is used in recombinant human growth hormone molecules. The C-terminus and N-terminus are fused with a hydrophilic amino acid sequence.
ACP-011, TransCon Human Growth Hormone, is the only human growth hormone prodrug designed with the patented "Transient Conjugation" technology in the world. The drug's mechanism of action is different from other technical long-acting growth hormone analogs. It can ensure the release of unmodified and active human growth hormone in the human body for 7 days, ensuring that the tissue distribution of active human growth hormone in the body is consistent with the once-daily recombinant growth hormone (rhGH).
Somatrogon (MOD-4023) uses conjugation technology to link the carboxy terminal peptide (CTP) of human chorionic gonadotropin (hCG) to recombinant human growth hormone molecule. Studies have shown that the half-life of CTP-containing fusion proteins increases. Therefore, two CTPs are fused to the C-terminal peptide of recombinant human growth hormone to form a new chemical structure of human growth hormone.
TV1106 uses growth hormone albumin binding technology to fuse human growth hormone and human albumin N-terminal to form a growth hormone substance with a conjugate structure, which has a longer clearance period in the blood.
HM10560A uses LAPSCOVERY (Long-acting Protein/Peptide Discovery Platform Technology), which combines the Fc fragments of human lgD and lgG4 with recombinant human growth hormone to form a long-acting fusion protein that can activate Janus kinase 2 in B lymphocytes Phosphorylation.
To sum up
At present, the main research and development trend of growth hormone in China has gradually become long-acting growth hormone. Among them, the fastest-growing long-acting growth hormone is Anke Bio's PEGylated recombinant human growth hormone injection and Weisheng medicine TransCon Growth Hormone (ACP-011), currently in clinical phase III.
This shows that domestic growth hormone will develop from ordinary injection to long-acting growth hormone formulations. In particular, Novo Nordisk, Anke Biotech, Xiamen Tebao and Weisheng Pharmaceutical will become the main competitors of the domestic growth hormone long-acting dosage form that impacts Jinsai Pharmaceutical's market position, and the long-acting growth hormone deployed by Pfizer will also be in the future. It is possible to lay out the Chinese market and squeeze into the domestic long-acting growth hormone market competition. In the future, the high-end long-acting growth hormone treatment field will break the dominance of Changchun Jinsai and form a situation where multiple markets are shared. At the same time, multiple participants After entering the market, the annual treatment cost of long-acting growth hormone will inevitably be reduced, thereby further expanding the market scale of long-acting growth hormone.
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