The Lancet Publishes Results from Gentium's Phase III Defibrotide Trial for the Prevention of VOD in Paediatric Patients

VILLA GUARDIA, Italy, Feb. 27, 2012 (GLOBE NEWSWIRE) -- Gentium S.p.A. (Nasdaq:GENT - News) (the "Company") announced today that results from a Phase III randomised controlled trial which evaluated Defibrotide for use in preventing hepatic veno-occlusive disease (VOD) in paediatric patients undergoing haemopoietic stem-cell transplantation (HSCT) were published in the medical journal, The Lancet (Vol 379). The results of Corbacioglu et al. show that Defibrotide leads to a 40% a reduction in the incidence of VOD thirty days after HSCT in patients receiving Defibrotide, compared with those who did not receive Defibrotide. Additionally, in allogeneic HSCT recipients (70% of study population), the incidence and severity of acute graft-versus-host disease (GvHD) were significantly lower in the Defibrotide arm. These finding supports the prophylactic use of Defibrotide in the HSCT transplant setting.

In a commentary article to the study, Drs. Uwe Platzbecker and Martin Bornhauser from Medizinische Klinik und Poliklinik I, Universitatsklinikum "Carl Gustav Carus" Dresden, Germany, conclude "Most importantly, defibrotide prophylaxis was well tolerated and did not lead to an increased risk of bleeding. Restriction by the legislative authorities means that there are few randomised trials in children, and thus Corbacioglu and colleagues' investigation is a pivotal European study, one that will hopefully change practice in paediatric patients and might also provide an impetus to investigate treatment options for adult patients."

About the Study Results

In the intention-to-treat analysis, 22 (12%) of 180 participants in the Defibrotide group had VOD by 30 days after HSCT compared with 35 (20%) of 176 controls (risk difference --7.7%, 95% CI --15.3 to --0.1; Z test for competing risk analysis p=0.048). In the per-protocol population, 18 (11%) of 159 participants in the Defibrotide group had VOD by 30 days after HSCT compared with 34 (20%) of 166 controls (risk difference --9.2%, 95% CI --17.0 to --1.3; Z test for competing risk analysis p=0.022). Additionally, in the intention-to-treat population, incidence and severity (grades 1--4) of acute graft-versus host disease were lower in the Defibrotide arm than they were in the control group (incidence p=0.006 and severity p=0.006 at 30 days and incidence p=0.005 and severity p=0.003 at 100 days after HSCT). The incidence of adverse events was similar between the Defibrotide and control arm, demonstrating that Defibrotide is well tolerated.

About the Study Design

The Phase III European pediatric prevention trial is a multi-center, open-label, randomized clinical trial to evaluate the prophylactic use of Defibrotide in pediatric patients undergoing stem cell transplantation who are at high risk for hepatic VOD. In the two-armed trial, patients were randomly assigned 1:1 to either receive Defibrotide prophylaxis or no prophylaxis (control arm) . Patients in the prophylaxis arm received 25 mg/kg/day of Defibrotide in four divided doses beginning at the time of conditioning. Patients in the control arm did not receive Defibrotide for VOD prophylactic measures. The primary endpoint of the study was development of VOD within 30 days post HSCT based on the modified Seattle criteria.

About VOD

Veno-occlusive disease is a potentially life-threatening condition, which typically occurs as a significant complication of stem cell transplantation. Certain high-dose conditioning regimens used as part of stem cell transplantation can damage the lining cells of hepatic blood vessels and result in VOD, a blockage of the small veins in the liver that leads to liver failure and can result in significant dysfunction in other organs such as the kidneys and lungs (so-called severe VOD). Stem cell transplantation is a frequently used treatment modality following high-dose chemotherapy and radiation therapy for hematologic cancers and other conditions in both adults and children. At present there is no approved agent for the treatment or prevention of VOD in the United States or the European Union.

About Gentium

Gentium S.p.A., located in Como, Italy, is a biopharmaceutical company focused on the development and manufacture of drugs to treat and prevent a variety of diseases and conditions, including vascular diseases related to cancer and cancer treatments. Defibrotide, the Company's lead product candidate, is an investigational drug that has been granted Orphan Drug status by the U.S. Food and Drug Administration (FDA) and Orphan Medicinal Product Designation by the European Medicines Agency, both to treat and to prevent VOD, as well as Fast Track Designation by the U.S. FDA to treat VOD.

Cautionary Note Regarding Forward-Looking Statements

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The Lancet Publishes Results from Gentium's Phase III Defibrotide Trial for the Prevention of VOD in Paediatric Patients