On March 30, 2016, the U. S. Food and Drug Administration approved Defitelio (defibrotide sodium, Jazz Pharmaceuticals, Inc.) for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstructive syndrome, with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT).
The efficacy of defibrotide sodium was investigated in 528 patients treated on three studies: two prospective clinical trials and an expanded access study. The patients enrolled had a diagnosis of hepatic VOD with multi-organ dysfunction after transplantation. They received defibrotide sodium 6.25 mg/kg intravenously every 6 hours until resolution of VOD.
The approval was based on survival at Day +100 after HSCT. The Day +100 survival rates for Study 1, Study 2 and Study 3 were 38% (95% 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 VOD with renal or pulmonary dysfunction who received supportive care or interventions other than defibrotide sodium.
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 VOD resolution or up to 60 days of treatment.
This application was granted Priority Review. A description of expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208114lbl.pdf
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