Gentium presents abstract on Defibrotide at EBMT Annual Meeting

Mar 24 2010

Gentium S.p.A. (Nasdaq: GENT) today announced that the abstract titled, "Defibrotide prevents hepatic VOD and reduces significantly VOD-associated complications in children at high risk: final results of a prospective phase II/III multicenter study," was presented on Sunday, March 21, 2010, at the opening session of the European Blood and Marrow Transplantation (EBMT) 36th Annual Meeting in Vienna. The abstract received the esteemed Van Bekkum Award for the best abstract submitted to the physician's program.  Dr. Selim Corbacioglu, Professor of Pediatrics, University of Regensburg (Germany) and Principal Investigator of the Pediatric Prevention trial, accepted the award and presented the final results of the study. 

This Phase II/III, randomized, controlled study evaluated the prophylactic use of Defibrotide in pediatric stem cell transplant (SCT) patients at high risk for veno-occulsive disease (VOD).  In the intent to treat analysis (ITT), which included 356 patients (180 patients in the prophylaxis arm and 176 in the control arm), Defibrotide demonstrated a 40% reduction in the incidence of VOD within 30 days after SCT, the primary endpoint of the study.  VOD incidence was 20% in the control arm and 12% in the prophylaxis arm>

In addition, a pre-specified analysis showed that the incidence and severity of acute graft versus host disease (GvHD) by day 100 in allogeneic SCT recipients was significantly reduced from 63% for the control arm to 45% for the prophylaxis arm>

"The results from the study demonstrated that Defibrotide reduced the incidence of VOD in high risk pediatric patients," stated Dr. Selim Corbacioglu. "SCT patients who develop VOD, regardless of its severity and despite prompt treatment, have a mortality rate four times greater than patients without VOD.  We are also very enthusiastic that Defibrotide has the potential to reduce the incidence and severity of acute GvHD, a life threatening complication, which is frequent in SCT and has limited treatment options.  We believe that Defibrotide could have a future role for the prevention of GvHD." 

"The Defibrotide VOD prevention study was the largest study performed in the pediatric SCT setting and its results have been included in the press conference of the EBMT," said Professor Dietger Niederwieser of University of Leipzig, Chairman of the opening session, President of the EBMT, and newly elected president of the Worldwide Network for Blood & Marrow Transplantation (WBMT). "The results of this study, which demonstrate a reduction in VOD as well as the potential beneficial effects on GvHD and renal failure, are consistent with the effects of endothelial protection and confirm the potential of Defibrotide in preventing transplant related toxicities."

"We are very encouraged by the recognition of this study by the leaders of the European hematology community," said Dr. Massimo Iacobelli, Scientific Director of Gentium. "We are fully engaged in preparing the regulatory submissions for the prevention and treatment of VOD."

Defibrotide's biological activity and mechanism of action were highlighted in a separate poster-presentation, "Defibrotide protects human microvascular endothelial cells from fludarabine-mediated pro-inflammatory and pro-apoptotic signals: a microarray (Affimetrix) analysis."  This study provides new biological insights on how Defibrotide might protect endothelial cells against chemotherapy-induced activation and cell death, without affecting the antileukemic effect of fludarabine and without affecting normal endothelium.

The satellite symposium "Defibrotide for the Prevention and Treatment of Hepatic VOD following stem cell transplant," was very well attended, featuring presentations by key opinion leaders Dr. Ernst Holler (University of Regensburg); Dr. Selim Corbacioglu (University of Regensburg); Dr. Paul Richardson (Dana Farber Cancer Institute, Boston, US), and Dr. Enric Carreras (University of Barcelona).  The symposium was chaired by Dr. Rob Soiffer (Dana Farber Cancer Institute, Boston, US).