Regulatory Decision Summary for Defitelio

Treatment IND Study 2006-05 was conducted upon request by the United States Food and Drug Administration (FDA) to provide access to defibrotide as an investigational new drug under an expanded access treatment protocol. Updated clinical data from this study continue to support a benefit in patients with severe veno-occlusive disease (VOD), both in the adult and pediatric populations. A percentage of 48.2% (247/512) of the patients with severe VOD following hematopoietic stem cell transplantation (HSCT) survived at Day +100; results are comparable in the adult and pediatric subgroups.

The updated safety profile is acceptable in the target patient population and is consistent with the labelled clinical data. Safety data was collected in a large number of patients with severe VOD (n>1200). The most common treatment-emergent adverse events (TEAEs) (> 10% of patients) were multi-organ failure (MOF) (12.2%) and hypotension (11.4%). The most common (≥ 5%) serious adverse events (SAE) were MOF (12.0%), VOD (7.5%), and respiratory failure (6.9%). A post-hoc analysis from Study 2006-05 indicated that increased mortality at Day +100 post-HSCT was associated with longer delays in defibrotide administration following a diagnosis of severe VOD. The reason for initiation delay following diagnosis was not assessed in this study.

Overall, based on the clinical data provided and with the risk minimization measures implemented, the benefits of Defitelio outweigh its risks for the indication sought. The benefit/risk profile of Defitelio continues to be favourable in the target patient population.