Gentium announced top-line results from a Phase 3 trial designed to evaluate the safety and efficacy of 25 mg/kg/day of defibrotide for the treatment of severe veno-occlusive disease (sVOD) in hematopoietic stem cell transplant (SCT) patients. The primary endpoint of this controlled, multicenter, open label, study was complete response at 100 days following SCT and utilized historical controls (patients who in the past received the best therapy and supportive care available at the time, but not defibrotide) as a comparator. Secondary endpoints included survival rate at 100 days and six months post SCT. One hundred twenty three patients with symptoms consistent with VOD were identified and then reviewed for eligibility in the historical control arm by the medical review committee, with 32 cases selected as having an unequivocal diagnosis of sVOD (graft versus host disease was ruled out) and met all protocol-required entry criteria. One hundred two patients were enrolled in the defibrotide treatment group and baseline characteristics were balanced between the two arms.
For the primary efficacy analysis on an intent to treat basis, 24% of patients in the defibrotide arm compared to 9% of patients in the historical control arm achieved complete response at 100 days (p-value = 0.015). For the secondary efficacy analysis on an intent to treat basis, 38% of patients in the defibrotide arm compared to 25% of patients in the historical control arm demonstrated survival at 100 days (p-value = 0.051). Thus, while the primary endpoint achieved a p-value less than 0.05 and the secondary endpoint showed a strong trend towards statistical significance, neither reached the level of significance required in the protocol for proof of efficacy with a single study.
Defibrotide is the sodium salt of a complex mixture of single-stranded oligodeoxyribonucleotides derived from porcine mucosal DNA. It is an orphan drug being studied for treatment of VOD, a potentially life-threatening condition, which typically occurs as an important complication of stem cell transplantation.
For more information visit www.gentium.com/Defibrotide.aspx.