The U.S. FDA recently announced that it has approved Ryoncil (remestemcel) developed by Mesoblast for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD) in children aged 2 months and older. The FDA's press release stated that this is the first FDA-approved mesenchymal stromal cell (MSC) therapy.

Ryoncil is a mesenchymal stromal cell produced by allogeneic bone marrow. It regulates T cell-mediated inflammatory responses by inhibiting T cell proliferation and downregulating the production of proinflammatory cytokines and interferons.

The safety and efficacy of Ryoncil were verified in a multicenter, single-arm study in which 54 pediatric patients with SR-aGVHD after allo-HSCT participated. Study participants received intravenous infusions of Ryoncil twice a week for a total of four weeks.

The main basis for efficacy is the remission rate and duration of remission 28 days after the start of treatment. Results showed that 16 participants (30%) achieved complete remission after 28 days of treatment with Ryoncil, while 22 participants (41%) achieved partial remission.

The most common adverse reactions to Ryoncil include infection, fever, bleeding, edema, abdominal pain and hypertension. In addition, complications such as hypersensitivity reactions, acute infusion reactions, transmission of infectious diseases, and ectopic tissue formation may occur after treatment.

Dr. Peter Marks, Director of the FDA's Center for Biologics Evaluation and Research, said: "Today's decision is a key milestone in the development of innovative cell therapies to treat life-threatening diseases, which have a very serious impact on patients, including children. The first approval of mesenchymal stromal cell therapy demonstrates the FDA's commitment to supporting the development of safe and effective products that are expected to improve the quality of life of patients who do not respond to other therapies."

▍Dosage form, dosage, contraindications and administration
Ryoncil can be used as a cell suspension for intravenous infusion with a target concentration of 6.68 × 106 MSCs/mL, in 3.8mL in a 6mL cryovial. Dosage and administration: The recommended dose of Ryoncil is 2 × 106 MSCs/kg/time intravenous injection, twice a week for four consecutive weeks, and the infusion should be at least 3 days apart. Evaluate the reaction 28±2 days after the first dose, and give further treatment as appropriate according to the table below. People with known allergies to dimethyl sulfoxide (DMSO), porcine and bovine proteins are prohibited from using it.

▍Ryoncil price expectations
First, let's review the history of Ryoncil. In 2012, Osiris' Prochymal was sold to Mesoblast in Australia and approved for marketing in Canada and New Zealand for the treatment of acute graft-versus-host disease. In 2015, Mesoblast cooperated with JCR to change its name to Temcell and market it in Japan. Temcell is used to treat graft-versus-host disease. The price of one Temcell is 40,000-50,000 RMB. 8 bags are a course of treatment. Adult patients are expected to take 2-3 courses of treatment, which is about 1 million RMB (123,000 to 185,000 USD). Therefore, we estimate that a bottle of Ryoncil containing 25 million cells will be priced at around RMB 50,000! The minimum cost of a course of treatment will not be less than RMB 400,000 (if your child is 2 years old and does not need more courses)! However, Jason McCarthy, an analyst at Maxim Group in the United States, believes that although the pricing/reimbursement of the drug in the United States has not yet been finalized, the market size and data can support premium pricing (estimated to be US$500,000 to US$1 million)!

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