What is the therapeutic effect of defibrotide?

Defitelio was first developed by Italy's Gentium Pharmaceuticals and was approved for marketing in the EU in October 2013. It was approved for marketing in the United States by the U.S. Food and Drug Administration (FDA) on March 30, 2016, under the trade name Defitelio. Defibrotide is the first drug approved by the U.S. FDA to treat severe hepatic veno-occlusive disease. It is used for adult or pediatric patients with hepatic venous obstruction (VOD) who have undergone blood or bone marrow hematopoietic stem cell transplantation (HSCT) and are accompanied by renal or lung function abnormalities. The drug has also received "orphan drug" designation.

Defibrotide is an adenosine receptor agonist with multiple effects. The adenosine A1/A2 receptors of endothelial cells are involved in the regulation of endothelial cells and the response of endothelial cells to injury. Defibrotide can act on these receptors to produce a variety of downstream effects. Defibrotide can also reduce the expression of cell adhesion molecules on the surface of endothelial cells, thereby reducing the adhesion of leukocytes to vascular endothelial cells and reducing the inflammatory damage of endothelial cells.

The recommended dose of Defibrotide is 6.25 mg/kg given every 6 hours as a 2-hour intravenous infusion. Treatment lasts for a minimum of 21 days. If signs and symptoms of VOD do not resolve after 21 days, continue treatment until resolution. Hypersensitivity reactions have occurred in less than 2% of patients treated with defibrotide. These reactions include rash, urticaria, and angioedema. If a severe hypersensitivity reaction occurs, discontinue defibrotide, treat with standard medical care, and monitor until symptoms resolve.

In one study, 19 patients with sHOVD were included. The dosage of defibrotide is 5~60mg/kg per day, intravenous infusion, and the median usage time is 15d (2-61d). The results showed that 42% of patients achieved complete remission (CR), and the overall survival (os) rate 100 days after transplantation reached 32%, and patients could tolerate defibrination well. Since then, multiple clinical trials have confirmed the effectiveness of defibrotide in the treatment of hepatic veno-occlusive disease.