Gentium S.p.A. updates on phase 3 trial of Defibrotide for severe veno-occlusive disease

Nov 19 2008

Gentium S.p.A. announced today interim results from an independent Data Safety Monitoring Board (DSMB) review of the Company's Phase 3 treatment trial of Defibrotide for Severe Veno-Occlusive Disease (VOD).

The DSMB reported that in order for the study to be 80% powered to detect a p-value of .01, the necessary statistical hurdle under the current protocol for FDA approval, the sample size should be increased to 160 patients in the treatment arm and 80 patients in the historical control arm. The DSMB also noted that a sample size of 102 patients in the treatment arm and 51 patients in the historical control arm would be needed to achieve a p-value of .05. Furthermore, the DSMB indicated that the data presented thus far do not raise any safety concerns and did not recommend that the trial be stopped for futility.

Gentium also announced today the preliminary results of an independent Medical Review Committee's (MRC) selection of historical control patients in the trial. Following the results of a prior DSMB meeting announced on June 5, 2008 in which the DSMB expressed concerns regarding the practical application of the criteria used to enroll historical control patients, the MRC met to re-review the criteria and eligibility of all historical control cases. After reviewing the available information, the MRC was only able to conclude that 32 out of the 86 patients initially included in the historical control arm definitively met the eligibility criteria and had a confirmed diagnosis of severe VOD. There are currently 102 patients enrolled in the treatment arm of the study.

"While we were hoping to be in a better position following the reviews of the DSMB and MRC concerning our Phase 3 trial, we remain committed to the development of Defibrotide," said Dr. Laura Ferro, CEO of Gentium. "We do not intend to enroll the additional number of patients required to achieve a p-value of .01; however, we are evaluating the possible enrollment of additional patients in the historical control arm, which would allow us greater potential to achieve a p-value that could be used as supportive data in favor of an approval of Defibrotide."

"We are currently in discussions with our corporate partner regarding the future development of Defibrotide and are also evaluating our strategic options for the Company," said Gary Gemignani, CFO of Gentium. "We continue to make progress in our European Pediatric Phase 2/3 prevention trial. To date, 345 out of 360 patients have been enrolled and we look forward to reporting results in 2009."

Veno-occlusive disease (VOD) is a potentially life-threatening condition, which typically occurs as an important complication of stem cell transplantation (SCT). Certain high-dose chemo-radiation therapy regimens used as part of SCT can damage the cells lining the hepatic blood vessels and so result in VOD, a blockage of the small veins of 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 with multiple organ failure). SCT is a frequently used treatment modality following high-dose chemotherapy and radiation therapy for hematologic cancers and other conditions in both adults and children. There is currently no approved agent for the treatment or prevention of VOD in the U.S. or the EU.