n Eu and US for prevention and treatment. Fast track in US for treatment following stem cell transplanation (5)
02/04/2009 11:04:23
PIII trials initiated. Granted fast track designation in US(1).
Trial or other data
Dec 13: Jazz Pharmaceuticals is to buy Gentium [24]
23/12/2013 08:52:58
Feb 12: Results published in the Lancet (Lancet, early online publication, 23 February 2012) of an RCT by the European Group for Blood and Marrow Transplantation that compared defibrotide prophylaxis vs standard of care in 356 paediatric patients at high risk of developing veno-occlusive disease after HSCT. 12% vs 20%, respectively, had veno-occlusive disease by 30 days after HSCT (primary endpoint); (risk difference −7.7%, p=0.0507). Patients in either group who developed veno-occlusive disease received defibrotide for treatment. Adverse events to 180 days after HSCT were similar in both groups (87 vs 88%).
24/02/2012 16:45:22
VOD is a potentially life-threatening condition which typically occurs as a significant complication of stem cell transplantation. Defibrotide has been used in its treatment as part of a large compassionate use program & ongoing named patient programs. The EU MAA is supported by several clinical trials, & includes data from the compassionate use program. If approved by the EMA, it will be the first drug licensed in the EU for treatment of VOD in either the treatment or prevention setting [8].
12/05/2011 11:30:09
Dec 09: The final results of the PII/III Pediatric Prevention trial and PIII Treatment trial were presented at the American Society of Hematology Conference (ASH). The company claim that both trials strongly trended toward statistical significance. The Prevention trial demonstrated a 40% reduction in the incidence of VOD at day 30 (p=0.0488 Competing Risk; p=0.0507 Kaplan-Meier) and the Treatment trial showed an improvement in complete response from 9% in the historical control arm to 24% in the defibrotide arm (p=0.0148). In the prevention trial, although not powered to assess mortality, a composite score measured as a secondary endpoint, incorporating VOD-associated morbidity (including respiratory failure, renal failure, encephalopathy) and mortality, significantly favored defibrotide prophylaxis (p=0.0340). Additionally, the incidence and severity of acute GvHD by day 100 in the allogeneic SCT recipients (246 patients) was reduced from 63% for the control arm to 45% for the prophylaxis arm (p=0.0044 for incidence of GvHD and p=0.0032 for severity). Defibrotide was well tolerated in both studies [6].
09/12/2009 10:16:27
Aug 09: Top-line results announced from an open label PIII trial to eva luate 25 mg/kg/day defibrotide for the treatment of severe veno-occlusive disease (sVOD) in haematopoietic stem cell transplant (SCT) patients. The results did not reach the protocol-specified levels of significance. On ITT analysis, 24% of 102 patients in the defibrotide arm vs 9% of patients in the historical control arm achieved the primary endpoint of complete response at 100 days (p-value 0.015), and 38% vs 25% respectively, demonstrated the secondary endpoint of survival at 100 days (p-value=0.051) [5].
19/08/2009 21:42:06
Mar 09: PII/III results from European Paediatric prevention trial - defibrotide in paediatrics undergoing stem cell transplantation (SCT) who are at risk for hepatic veno-occlusive disease (VOD). Intention to treat populatio n= 180 pts in treatment ar |
