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FDA Approves Defibrotide Sodium for the Treatment of Hepatic Veno-Occlusive Disease Following Hematopoietic Stem Cell Transplantation

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On March 30, 2016, the U.S. Food and Drug Administration (FDA) approved defibrotide sodium (Defitelio) for the treatment of adult and pediatric patients with hepatic veno-occlusive disease, also known as sinusoidal obstructive syndrome, with renal or pulmonary dysfunction following hematopoietic stem cell transplantation. This is the first FDA-approved therapy for treatment of severe hepatic veno-occlusive disease, a rare and life-threatening liver condition.

“The approval of [defibrotide sodium] fills a significant need in the transplantation community to treat this rare but frequently fatal complication in patients who receive chemotherapy and hematopoietic stem cell transplantation,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research.  

Clinical Trials

The efficacy of defibrotide sodium was investigated in 528 patients treated on three studies: two prospective clinical trials (study 1 and study 2) and an expanded access study (study 3). The patients enrolled had a diagnosis of hepatic veno-occlusive disease with multiorgan dysfunction after transplantation. They received defibrotide sodium at 6.25 mg/kg intravenously every 6 hours until resolution of veno-occlusive disease.

The approval was based on survival at 100 days after hematopoietic stem-cell transplantation. The day +100 survival rates for study 1, study 2, and study 3 were 38% (95% confidence interval [CI] = 29%–48%); 44% (95% CI = 33%–55%); and 45% (95% CI = 40%–51%), respectively. Based on published reports and analyses of patient-level data, the day +100 survival rates were 21% to 31% for patients with hepatic veno-occlusive disease with renal or pulmonary dysfunction who received supportive care or interventions other than defibrotide sodium.

Toxicity and Administration

In vitro defibrotide sodium has profibrinolytic activity. The use of defibrotide sodium is contraindicated in patients being treated concurrently with anticoagulants or fibrinolytic therapies. Hemorrhage and hypersensitivity reactions are the major potential adverse reactions. The most common adverse reactions (incidence greater than or equal to 10%) were hypotension, diarrhea, vomiting, nausea, and epistaxis.

The recommended dose and schedule for defibrotide sodium is 6.25 mg/kg intravenously every 6 hours given as a 2-hour infusion for at least 21 days, and continued until veno-occlusive disease resolution or up to 60 days of treatment.

Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208114lbl.pdf.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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