Positive data from a phase 3 pivotal study of defibrotide (Jazz Pharmaceuticals), a deoxyribonucleic acid derivative, have been published online in Blood, the journal of the American Society of Hematology. The findings demonstrated that treatment with defibrotide in patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome, with multiorgan failure (MOF) after hematopoietic stem-cell transplantation (HSCT) was associated with a statistically significant improvement in day +100 survival and in the complete response (CR) rate by day +100 compared with historical controls.
In the U.S., defibrotide is an investigational drug for the treatment of patients with hepatic VOD with multiorgan dysfunction, defined as renal or pulmonary dysfunction, after HSCT. Defibrotide was granted an orphan drug designation by the FDA in May 2003 and has a fast-track designation. A new drug application is under review by the FDA. Hepatic VOD can be a life-threatening complication of HSCT. Hepatic VOD with MOF has been associated with an 84% mortality rate.
The phase 3 study investigated the safety and efficacy of defibrotide in adult and pediatric patients with established hepatic VOD with MOF. A total of 132 patients treated with defibrotide (25 mg/kg per day) were compared with 32 historical controls identified from review of medical charts of HSCT patients by an independent medical review committee, blinded to outcome.
Defibrotide was associated with a statistically significant improvement in day +100 post-HSCT survival, the study’s primary endpoint, compared with the historical controls. The estimated between-group difference in day +100 survival was 23% (P = 0.0109). The difference in CR rates by day +100 after HSCT, a secondary endpoint, resulted in an estimated between-group difference of 19% (P = 0.0160). The median duration of treatment with defibrotide was 21.5 days.
Hypotension was the most common adverse event in both treatment groups (39% of defibrotide-treated patients and 50% of the 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.
Sources: Jazz Pharmaceuticals; February 1, 2016; and Blood; January 29, 2016.