PlatExcell Biotech's AmyMaxa Becomes China's First Approved Domestic Stem Cell Therapy

On January 2, the NMPA website announced that Platinum Biotech Excellence (Beijing) Co., Ltd. (hereinafter referred to as Platinum Biotech Excellence) had received marketing approval for its stem cell therapy, emicizumab, for the treatment of steroid-refractory acute graft-versus-host disease (aGVHD) primarily involving the gastrointestinal tract in patients aged 14 years and older, making it the first stem cell therapy approved for marketing in China.

It is reported that Aimaituosai Injection is a human umbilical cord mesenchymal stem cell injectable. In May 2024, Platinum Biotech Excellence (Beijing) Co., Ltd. obtained China’s first drug production license for stem cell products. Marketed as a prescription drug, it will be used in hospitals under physician prescriptions to treat corresponding indications.

Acute graft-versus-host disease (aGVHD) is a multi-organ syndrome that occurs after allogeneic hematopoietic stem cell transplantation (allo-HSCT), in which donor-derived lymphocytes attack recipient tissues, manifesting primarily as tissue inflammation and fibrosis affecting the skin, gastrointestinal tract, liver, lungs, and mucosal surfaces. The approval of emicizumab will provide a novel treatment option for numerous patients with aGVHD.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the key approaches to curing malignant and non-malignant hematologic disorders. With the growing number of patients suffering from hematologic diseases such as acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), myelodysplastic syndromes, multiple myeloma (MM), and lymphoma, the volume of transplantation procedures continues to surge dramatically.According to statistics, in 2023, 216 medical institutions in China performed a total of 14,952 allogeneic hematopoietic stem cell transplantation (allo-HSCT) procedures, ranking first globally.

Among these, acute graft-versus-host disease (aGVHD) is a major cause of non-relapse mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Data show that the incidence rates of grade II–IV aGVHD were 39.5%, 24.0%, and 40.3% in haploidentical, HLA-identical sibling, and matched unrelated donor HSCT, respectively; the incidence rates of grade III–IV aGVHD were 11.4%, 7.7%, and 13.5%, respectively.

In addition to the high incidence of complications, the prognosis is also unfavorable. The 1-year overall survival rate for patients with grade II acute graft-versus-host disease (aGVHD) is 70%, while that for patients with grade III–IV aGVHD is 40%. aGVHD accounts for 17%–20% of causes of death among post-transplant patients.

However, there is a significant unmet clinical need in the current treatment landscape for acute graft-versus-host disease (aGVHD). First-line therapy for aGVHD consists of glucocorticoids, with an efficacy rate of only approximately 50%. Approximately half of patients are steroid-refractory, i.e., have SR-aGVHD, and their long-term survival rate is less than 20%.

Patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD) should initiate second-line therapy as soon as possible, including JAK inhibitors, alemtuzumab, alpha-1 antitrypsin (AAT), basiliximab, mesenchymal stem cells (MSCs), and daclizumab. Currently, there is no standard clinical treatment regimen; generally, second-line agents are added while maintaining effective glucocorticoid concentrations, and if one second-line agent proves ineffective, it is switched to another.

Emicizumab Injection, recently approved for marketing, is a human umbilical cord mesenchymal stem cell injection. Mesenchymal stem cells possess multipotency and immunomodulatory properties, and have been successfully used in the treatment of tissue repair and autoimmune diseases, including acute graft-versus-host disease (aGVHD).Multiple studies have demonstrated that mesenchymal stem cells (MSCs) are safe and effective for the prevention and treatment of graft-versus-host disease (GVHD), and they have been recommended as a Level A-II evidence for the treatment of acute GVHD (aGVHD).Furthermore, MSCs can reduce the adverse effects of second-line drugs, such as bone marrow toxicity and infections.

In fact, mesenchymal stem cell therapy has been applied in the field of GVHD for a considerable period.

In 2005, Prochymal, a stem cell drug developed by Osiris Therapeutics, was granted orphan drug designation by the U.S. FDA for the indication of GVHD. In 2013, it was transferred to the Australian company Mesoblast and renamed Ryoncil. After a prolonged period of standard-setting and clinical trials, it was approved in Japan in 2015 under the new brand name Temcell for the treatment of acute GVHD (aGVHD). The price was set at 860,000 yen (approximately RMB 50,000) per bag, with eight bags per treatment course.

In August 2020, the FDA Oncologic Drugs Advisory Committee voted 9:1 in support of Ryoncil’s efficacy in pediatric patients, but subsequently recommended further research. In August 2023, although the FDA responded to Mesoblast’s application, it still requested additional data. In response, Mesoblast resubmitted new clinical trial data, including a matched study in children with high-risk disease and four-year survival data from 51 pediatric patients, both of which demonstrated significant efficacy.

On December 18, 2024, Ryoncil received FDA approval, becoming the first mesenchymal stem cell (MSC) therapy approved in the United States for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGvHD). The approved indication is for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in pediatric patients aged 2 months and older.

Notably, Aimaituosai Injection also underwent a prolonged R&D process. In March 2013, Platinum Biotech Excellence submitted an Investigational New Drug (IND) application in China for its umbilical cord-derived mesenchymal stem cells; however, the clinical trial was not publicly disclosed until June 2020. In May 2024, Platinum Biotech Excellence received China’s first drug production license for stem cell products. In June, Aimaituosai was included in the Center for Drug Evaluation’s (CDE) priority review and approval program, and the New Drug Application (NDA) was formally submitted in the same month.

Billed as the “core technology of the third medical revolution,” the “potential dawn of cell therapy,” and “universal cells,” stem cell technology has been one of the hottest sectors in the biopharmaceutical industry since the 21st century. According to an analysis report by Precedence Research, the global stem cell market size was $15 billion in 2023 and is projected to grow to approximately $48.83 billion by 2034, with a compound annual growth rate (CAGR) of about 11.3% from 2024 to 2034.

Meanwhile, the stigmatization of stem cell therapeutics has become rampant, with these products often hyped as miracle cures that can “cure all diseases” and “reverse aging.” Amidst such widespread rumors, products backed by robust regulatory compliance, adherence to standards, and solid clinical data have become key to rectifying market practices and validating product efficacy.

In China, the 2018 “Technical Guidelines for Research and Evaluation of Cell Therapy Products (Trial)” clarified that cell-based products can be registered and regulated under the drug review process. Stem cell products developed via the drug registration pathway are referred to as new stem cell drugs, which generally need to undergo two stages: Investigational New Drug (IND) application and New Drug Application (NDA). Since then, research, development, and regulatory submissions of domestically produced stem cell drugs have surged, with various policies and guidelines continuously keeping pace with these developments.

According to the “Annual Report on Clinical Trial Progress of New Drug Registration in China (2023)” released by the Center for Drug Evaluation, National Medical Products Administration, a total of 81 clinical trials for cell and gene therapy products were registered in China in 2023, representing a nearly twofold increase from the 46 trials registered in 2022.

In 2024, the field of stem cell therapeutics witnessed several significant developments: in January, the “Technical Guidelines for Clinical Trials of Mesenchymal Stem Cells in the Prevention and Treatment of Graft-versus-Host Disease (Trial)” were released; in May, the Beijing Municipal Medical Products Administration issued China’s first Drug Production License for stem cells; and in November, the Beijing Municipal Healthcare Security Administration announced an expansion of the scope of medical insurance reimbursement for stem cell transplantation.

Globally, stem cell regulatory frameworks are primarily divided into two categories. The first category involves registration as new drugs, regulated by drug supervision and administration authorities, as seen in China, the European Union, and the United States. The second category involves classified registration as either new drugs or medical technologies, regulated respectively by drug supervision and administration authorities and health supervision and administration authorities, exemplified by Japan’s dual-track regulatory model.

Prior to the approval of Ryoncil and emraclidine, there were no approved stem cell drugs on the market in China or the United States. Previously, a total of 11 stem cell drugs had been approved globally, including five in South Korea, two in the European Union, and two in Japan, with indications covering subcutaneous tissue defects, acute myocardial infarction, Crohn’s disease, and other conditions.

Interestingly, Japan’s first approved stem cell product remains Temcell, indicated for the treatment of graft-versus-host disease (GVHD), which was approved in the United States in December 2024 under the name Ryoncil. In their initial forays into stem cell therapies, countries have consistently opted for mesenchymal stem cell products with robust clinical data and strict regulatory compliance.

Since then, Japan’s dual-track regulatory model has undergone nine years of development. According to a September 2022 report in *Cell Stem Cell*, there were 3,467 cell therapy products listed on the website of Japan’s Ministry of Health, Labour and Welfare, involving 2,377 medical institutions. These therapies are categorized as Class I, II, or III regenerative medicine products, with a multi-institutional, multi-tiered approval process established according to risk levels. The most common indications were dental diseases (1,513 products) and cancer (1,215 products). In addition, 513 products were approved for non-disease treatments, such as cosmetic dermatology, anti-aging, and plastic surgery.

In China, a total of 142 stem cell drug applications had been accepted by the CDE as of 2024.Innovative pharmaceutical companies are extensively deploying in the field of stem cell therapy, repair, and regeneration, covering areas such as spinal cord injury, Type 1 diabetes, Parkinson's disease, Alzheimer's disease, heart disease, stroke, burns, cancer, and osteoarthritis. Among them, multiple biotech firms have targeted differentiated indications including chronic periodontitis, inflammatory bowel disease, refractory systemic lupus erythematosus, and moderate-to-severe chronic plaque psoriasis.

Reference Materials:

Cell Therapy Junior: “China’s ‘Dual-Track’ System for Stem Cells: Latest Summary of Clinical Filing and New Drug Development Projects”

Health界: "The Eve of the Explosion of New Stem Cell Drugs in China: Is a Golden Decade About to Begin?"

TMTPost: Behind the Issuance of the First Stem Cell Therapy Approval, the “First Drug” Has Accelerated, with Capital Still Concentrating in the Upstream Industry