Date: 2016-02-01
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in Blood
Company: Jazz Pharmaceuticals (Ireland)
Product: Defitelio®(defibrotide)
Action
mechanism: Defibrotide is the sodium salt of a complex mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It has protective effects on vascular endothelial cells, particularly those of small vessels. It has extensive beneficial pharmacological effects owing to its antithrombotic, anti-inflammatory and antiischemic properties.
Disease: severe veno-occlusive disease (VOD) in patients undergoing haematopoietic (blood) stem-cell transplantation
Therapeutic area: Cardiovascular diseases - Rare diseases
Country:
Trial
details: The phase 3 study investigated the safety and efficacy of defibrotide in adult and pediatric patients with established hepatic VOD/SOS with MOF. Patients (n=102) given 25 mg/kg/day defibrotide were compared with 32 historical controls identified from review of medical charts of HSCT patients by an independent medical review committee, blinded to outcome.
Latest
news: * On February 1, 2016, Jazz Pharmaceuticals announced that data from the phase 3 pivotal study of defibrotide were published online in Blood, the Journal of the American Society of Hematology (ASH). The data demonstrated that defibrotide use in patients with hepatic veno-occlusive (VOD), also known as sinusoidal obstruction syndrome (SOS), with multi-organ failure (MOF) post-hematopoietic stem-cell transplantation (HSCT) was associated with a statistically significant improvement in Day +100 survival and in rate of complete response (CR) by Day +100, compared with rigorously selected historical controls. Defibrotide was associated with a statistically significant improvement in Day +100 post-HSCT survival, the primary endpoint, compared to the historical controls. The estimated between-group difference in Day +100 survival was 23.0% (95.1% confidence interval (CI): 5.2%-40.8%; P=.0109), using a propensity-adjusted analysis. The difference of complete response (CR) rates by Day +100 post-HSCT, a secondary endpoint, resulted in an estimated between-group difference adjusted for propensity score of 19.0% (95.1% CI: 3.5 - 34.6; P=.0160). Median duration of treatment with defibrotide was 21.5 days. Hypotension was the most common adverse event in both groups (39.2% with defibrotide and 50.0% for historical controls). Related adverse events included hemorrhage and hypotension. There was no difference in the incidence of common hemorrhagic events between defibrotide and the historical controls.
