Defibrotide promising for stem cell transplant complication

Last Updated: 2016-02-09

By David Douglas

NEW YORK (Reuters Health) - Defibrotide improves survival in hepatic veno-occlusive disease (VOD) -- also known as sinusoidal obstruction syndrome (SOS) -- in hematopoietic stem cell transplantation (HSCT) patients, according to U.S. and European investigators.

As Dr. Paul G. Richardson told Reuters Health by email, "Defibrotide has been shown in this pivotal phase 3 study to provide meaningful clinical benefit to patients with severe VOD/SOS and advanced multi-organ failure (MOF), which, as a potentially life-threatening complication of HSCT, has no other approved treatment. It therefore constitutes an urgent unmet medical need both for adults and children in this setting."

In a January 29 online paper in Blood, Dr. Richardson of the Dana-Farber Cancer Institute, Boston and colleagues reported that they studied 102 patients with this orphan disease. The patients were given defibrotide 25 mg/kg/day, and the researchers compared outcome with that of 32 matched historic controls.

In all, 39 patients (38.2%) in the defibrotide group and eight (25.0%) in the control group were alive at Day+100 post-HSCT.

Using a propensity-adjusted analysis including prognostic factors such as age, the estimated between-group difference in survival was 23.0% (p=0.0109). Similarly, complete response rates were calculated to be 25.5% for defibrotide and 12.5% in the controls.

Adverse events included hemorrhage and hypotension, but the researchers wrote that the agent "was generally well-tolerated with manageable toxicity."

"These results," continued Dr. Richardson, "demonstrated encouraging efficacy as reflected by significant improvements in D+100 survival post HSCT and complete response, as well as favorable tolerability. As such, these data provided the basis for the approval of defibrotide as treatment for VOD/SOS in Europe and will hopefully result in regulatory approval here in the United States."

In October 2013, the European Commission granted marketing authorization for use of defibrotide (Defitelio, Jazz Pharmaceuticals) under exceptional circumstances for the treatment of severe hepatic VOD in patients undergoing HSCT therapy. The agent received an approval in Israel in May 2015 for the same indications.

In September 2015, Jazz announced that the Food and Drug Administration has accepted for filing with priority review its recently submitted new drug application (NDA) for defibrotide. Based on timelines established by the Prescription Drug User Fee Act (PDUFA), FDA review of the NDA is expected to be completed by March 31, 2016.

The study was funded by Gentium, now Jazz Pharmaceuticals. Dr. Richardson and other authors have relationships with Jazz Pharmaceuticals. Three of the authors are employed by Jazz and another worked for Gentium at the time of the study.

SOURCE: http://bit.ly/1TP3FNM

Blood 2016.