Italian drugmaker Gentium has pulled its US marketing application for defibrotide, a drug for veno-occlusive disease (VOD), after it became clear that the Food and Drug Administration would not accept the filing.
VOD is a condition in which some of the veins in the liver are blocked as a result of cancer treatments, such as chemotherapy or radiation treatments, that are given prior to stem cell transplantation.
Defibrotide - Gentium's lead product candidate - is designed to protect vascular endothelial cells from damage in VOD thanks to its antithrombotic, anti-inflammatory and anti-ischaemic properties. The drug is being developed for hepatic VOD, a particularly severe form of the condition which is associated with multiple-organ failure and high rates of morbidity and mortality, sometimes as high as 90%.
Gentium submitted defibrotide for approval in the USA on the strength of a multicentre Phase III study looking at treatment and prevention of hepatic VOD, a Phase II dose-ranging study and interim data from an expanded access programme in the USA, but has been told by the FDA that its dossier does not pass muster.
The FDA "raised concerns regarding the completeness of the datasets for both the treatment and prevention studies [and] requested … additional quality reviews of the original datasets and databases," said Gentium in a statement.
The agency has also asked for additional details regarding the conduct and monitoring of the trials by the independent review committee, it added.
Shares in the Nasdaq-listed company fell sharply on the news, closing some 22% down at $6.85 yesterday.
Gentium has also filed a marketing authorisation application with the European Medicines Agency for the prevention and treatment of hepatic VOD in adults and children undergoing stem-cell transplantation therapy. The application was accepted and granted an accelerated review by the EMA on May 25.
There is currently no approved agent for the treatment or prevention of VOD in the US or the EU.