The latest inventory ｜ How many stem cell drugs have been listed in the world？
At the 2020 China Biotechnology Innovation Conference, experts pointed out that stem cells, as strategic resources, are strategic, public-spirited and supportive, in which the strategy is for national security and future competition, the public-spirited is for population health and social development, and the supportive is for scientific, technological, industrial and economic development. It is an important measure to ensure people’s health to collect, store, develop, utilize and share strategic stem cell resources and promote clinical transformation.
Stem cell resources are important strategic resources of the country. How to safely and effectively preserve China’s special, unique and rare human biological resources is of great significance for promoting China’s population health, maintaining the safety of life resources and treating major diseases.
One of the important values of stem cells is their application in disease treatment.
Professor Thomas C. Sudhof, winner of the Nobel Prize in Physiology or Medicine, once said, "We can control the disease and stem cells are a very good treatment. " Stem cell research will bring new hope to the problems that traditional medical treatment can’t solve.. "
Internationally, the United States, South Korea, Japan, the European Union and so on have approved stem cell therapy products listed, and stem cell therapy for diseases is becoming a more extensive reality.
By April, 2021, more than 1,200 clinical trials of mesenchymal stem cells were retrieved from ClinicalTrials.gov website.
In recent years, this number has continued to increase, indicating that the importance of mesenchymal stem cells is increasing.
At present, the research and development of stem cell drugs in China is becoming more and more standardized, attracting a lot of capital and talents. At the moment when the results are about to blow out, we look forward to this market by combing the foreign mesenchymal stem cell drugs.
According to incomplete statistics, there are 18 mesenchymal stem cell products that have been approved for marketing in the world, and 10 products meet the definition of drugs.
18 products related to mesenchymal stem cells (including orphan drugs, conditionally approved drugs, medical products, etc.); The date and country of approval are the first approval; Multistem is not counted, because its official website claims that the drug is not mesenchymal stem cells.
01
More flowers, Mesoblast
Prochymal: graft versus host disease
Country: USA, Canada, New Zealand
Date: May 2010
Cell type: bone marrow mesenchymal stem cells
Indications: graft versus host disease, Crohn’s disease
Price: $200,000/course of treatment
Initially, the FDA of the United States approved it as an orphan drug for the treatment of type I.
In 2012, Prochymal was sold to Mesoblast in Australia, and was approved for marketing in Canada and New Zealand to treat acute graft-versus-host disease.
In 2015, Mesoblast cooperated with JCR and renamed it Temcell to be listed in Japan.
Temcell: graft versus host disease
Country: Japan
Date: February 2016
Cell type: bone marrow mesenchymal stem cells
Indications: graft versus host disease
Price: about $120,000/course of treatment.
As mentioned above, Temcell was formerly Prochymal of Osiris Company and Ryoncil of Mesoblast Company.
In 2019, TEMCELL was approved to treat epidermolysis bullosa and neonatal hypoxic-ischemic encephalopathy.
In JCR’s financial report, Temcell’s sales revenue was about 18 million US dollars in 2018 and 28 million US dollars in 2019.
MPC: bone repair
Country: Australia
Date: July 2010
Cell type: autologous mesenchymal precursor cells
Indications: bone repair
Price: unknown
In 2010, the MPC(Mesenchymal Precursor Cell) independently developed by Mesoblast was approved for listing in Australia for the repair and regeneration of damaged tissues.
Mesoblast’s current market value is about $1 billion, and its business income of $6.6 million in fiscal year 2020 comes entirely from Temcell, mainly from milestone payments ($25 million) from China, Japanese and other partners.
02
Try first, Korea FDA
CellGram: acute myocardial infarction
Country: Korea
Date: July 2011
Cell type: autologous bone marrow mesenchymal stem cells
Indications: Acute myocardial infarction
Price: $15,000
CellGram was used by coronary angioplasty within 72 hours after chest colic to improve the left ventricular blood cell count in patients with myocardial infarction. After 6 months of treatment, the measurement showed that each treatment improved the left ventricular ejection fraction by 6%.
By 2017, this therapy has created sales of about $7.8 million. However, CellGram failed to meet the requirements of treating 600 patients within a six-year period, and Pharmicell applied to reduce the minimum number of patients to 60, which was rejected.
Some industry observers speculate that South Korea will cancel its approval, but this is the first stem cell drug in South Korea. "The cancellation of approval will have a harmful impact on the national reputation, and we must make a cautious decision."
Cartistem: degenerative arthritis
Country: Korea
Date: January 2012
Cell type: umbilical cord blood mesenchymal stem cells
Indications: Degenerative arthritis and knee cartilage injury.
Price: 19,000-21,000 USD
In the eight years since Cartistem was put on the market, the cumulative sales have exceeded 18,000 doses.
From 2017 to 2020, Cartistem has sold more than 10 billion won (about 9 million US dollars) for four consecutive years, which is obviously better than the other three stem cell drugs approved by South Korea (the annual sales are less than 5 billion won).
Medipost quarterly sales trend (millions of won, source: Medipost)
Researchers such as Kim SJ conducted a retrospective analysis of 128 product users, and found that after two years of follow-up, the pain and function of these patients were improved, which was statistically significant.
At present, the product has completed phase I and IIa clinical trials in the United States, and phase II clinical trials are being carried out in Japan.
Cupistem: Crohn’s disease
Country: Korea
Date: January 2012
Cell type: autologous adipose-derived mesenchymal stem cells
Indications: complex Crohn’s disease complicated with anal fistula
Price: 3000-5000 USD
Cupistem is used to reduce inflammation of Crohn’s fistula.
In a phase II clinical trial, 43 patients were evaluated for fistula healing after 12 months, and 80.8% of them showed complete fistula healing. After 24 months, 75% of these patients were completely closed, showing sustainable safety and therapeutic effect.
NeuroNATA-R: amyotrophic lateral sclerosis
Country: Korea
Date: July 2014
Cell type: autologous bone marrow mesenchymal stem cells
Indications: amyotrophic lateral sclerosis, motor neuron disease
Price: USD 18,000-72,000 (according to weight)
NeuroNATA-R is a stem cell therapy provided by Corestem Company of South Korea. Mesenchymal stem cells need to be collected from the patient’s own bone marrow four weeks before each injection of stem cells.
In the phase I clinical trial to evaluate the safety, 7 patients received intrathecal injection twice and were followed up for 12 months. The research shows that it has good security.
03
Not to be outdone, Japan and India
Stempeucel: Severe limb ischemia
Country: India, ratified by EU.
Date: June 2015
Cell type: bone marrow mesenchymal stem cells
Indications: thromboangiitis obliterans
Price: $2,200 (2017)
In 2015, Stempeucel was approved by the European Medicines Agency (EMA) as an orphan drug to treat thromboangiitis obliterans.
In 2017, the General Administration of Drug Administration of India (DCGI) granted Stempeucel a limited marketing license to treat patients with severe limb ischemia caused by Buerger’s disease. In 2020, DCGI completed the formal approval.
The research and development of Stempeucel lasted for 12 years and finally became the first allogeneic cell therapy product approved for commercial use in India.
Alofisel: Crohn’s disease
Country: Japan, EU ratification
Date: March 2018
Cell type: adipose-derived mesenchymal stem cells
Indications: complex perianal fistula in patients with Crohn’s disease
Price: about $70,000/course.
In 2018, Takeda, a Japanese pharmaceutical giant, and TiGenix, a Belgian stem cell company, jointly announced that EMA had approved Alofisel (CX 601) for the treatment of Crohn’s disease complicated perianal fistula whose fistula failed to respond to at least one traditional or biological therapy.
However, Alofisel encountered some difficulties in obtaining the so-called third-level approval, which is a term used to refer to national payer insurance. For example, NICE in the UK refused to recommend Alofisel on the grounds that it did not benefit much from clinical trials.
In 2019, Takeda decided to adopt value-based pricing in Europe. In other words, if patients do not improve, they will bear part or all of the expenses.
In the fiscal year ending March 31st, 2020, Takeda earned about $350,000 from Alofisel.
Stemirac: spinal cord injury
Country: Japan
Date: 2018-12
Cell type: autologous bone marrow mesenchymal stem cells
Indications: spinal cord injury
Price: $135,000
The listing of Stemirac is somewhat controversial. It only did phase II clinical trials, and it was conditionally approved and included in the national health insurance.
This move was criticized by Nature, who thought that there was no control group in its clinical trial, and there were only 13 subjects in the treatment group. The Japanese side responded that setting up a control group may cause moral problems.
According to an article in 2019, Stemirac will bring about $3.4 million in revenue to Nipro every year in the next nine years.
04
The pace of clinical treatment of stem cells in China is accelerating!
According to the data of National Medical Products Administration Drug Evaluation Center, up to now, eight new drugs of mesenchymal stem cells have been applied for clinical approval in China, and the indications are acute graft-versus-host disease, rheumatoid arthritis, ischemic stroke, knee osteoarthritis and diabetic foot.
Source: CDE
At present, the supervision of stem cell therapy in China adopts a "dual-track management model". National Health Commission mainly manages clinical research conducted by medical institutions, and the Food and Drug Administration is mainly responsible for stem cell therapy products that are applied for marketing after clinical trials are completed according to drugs.
In recent two years, the clinical application of stem cells in China has been standardized under the "dual-track management model".Up to now, 74 stem cell clinical research projects have passed the record of National Health Commission. Eight applications for new stem cell drugs have been approved by the Food and Drug Administration..
Compared with the past few years, the clinical transformation of stem cells in China is developing with a brand-new trend, and the blank of domestic stem cell listed drugs is expected to be filled faster.
At present, in the field of stem cell transformation, the research in China mainly focuses on stem cell bank, stem cell drug application, preclinical research and clinical trials. The gradual improvement of regulatory policies has pushed the clinical transformation of stem cells in China to a new development situation.
First, China has entered a new stage of development of new stem cell drugs.The promulgation of "Technical Guiding Principles for Research and Evaluation of Cell Therapy Products (Trial)" clarified the standard of stem cell therapy as a drug declaration, and at the same time, the new drug approval system of "60-day clinical trial implied permission" provided new development opportunities for the research and development and declaration of new stem cell drugs in China.
Second, the national "stem cell and transformation research" focuses on promoting the development of stem cell therapy drugs.For example, one of the assessment objectives pointed out in the key special declaration guidelines is to develop cell therapy drugs for a major or rare disease, apply for registration of new stem cell drugs and apply for clinical approval of stem cells.
Third, the policy encourages the strength of comprehensive enterprises to promote the clinical transformation of stem cells.In the past two years, some domestic policies explicitly support qualified 3A hospitals to cooperate with qualified social forces to declare and carry out stem cell clinical research, that is, to support and encourage qualified social forces or preparation institutions (enterprises) to join the stem cell industry and jointly promote the clinical application and development of stem cells. The promotion of enterprise innovation forces has accelerated the development and application of stem cells in China.
At present, there are still many diseases that need innovative therapies to solve the unmet clinical needs, and the expansion of indications for new stem cell drugs is precisely to meet these needs.
05
Perinatal tissue stem cells have gradually become mainstream.
Perinatal tissue is one of the largest sources of mesenchymal stem cells, and it has become a popular source of stem cells for new drug research and development. Mesenchymal stem cells derived from perinatal tissues have the advantages of multi-directional differentiation potential, immunological characteristics, convenient and harmless material collection, wide sources and easy industrial preparation, which has become a new trend of medical development. At present, more than 60% of the new stem cell drugs that have obtained clinical approval in China use mesenchymal stem cells derived from perinatal tissues.
In the treatment of severe patients in COVID-19, mesenchymal stem cells derived from perinatal tissues have also shown a good effect. Domestic research reports show that the critically ill patients in COVID-19 were transferred out of ICU after 9 days of reinfusion of mesenchymal stem cells from perinatal tissues, and most vital signs and clinical trial indicators returned to normal, and both throat swab tests were negative for Covid-19.
In recent years, immune cells derived from perinatal tissues have gradually become a research hotspot. Previously, the FDA approved the clinical trial of immune cells derived from human placental stem cells to treat COVID-19, which was developed by Celularity, a biotechnology company in New Jersey, USA.
In the early trial, as many as 86 patients with symptomatic COVID-19 will be treated to evaluate the safety of the treatment and the ability to prevent patients from getting worse.
Internationally, placental cell therapy products are also accelerating the pace of entering the market. For example, placenta-derived adherent cell PLX-PAD, which has attracted much attention in recent years, is being designed to treat patients who do not need tissue or genetic matching.
This therapy has passed the accelerated approval routes in the United States and the European Union, including the quick approval qualification of the US FDA and the Adaptive Pathways program of the EU EMA, for the treatment of limb ischemia. In addition, PLX-PAD has also been used in clinical research of other indications, including intermittent claudication, orthopedic indications, pulmonary hypertension and women’s health, and some of them have entered clinical phase III.
At present, China’s stem cell industry has formed a huge market scale. With the clinical transformation and market development, the era of stem cells benefiting patients in China will also come.