The FDA has approved defibrotide sodium (Defitelio) for the treatment of hepatic veno-occlusive disease following hematopoietic stem cell transplantation in both adults and children.
The US Food and Drug Administration (FDA) has approved defibrotide sodium (Defitelio) for the treatment of hepatic veno-occlusive disease (VOD) following hematopoietic stem cell transplantation (HSCT) in both adults and children. This is the first drug approved for severe hepatic VOD, which can be life-threatening.
“VOD is a devastating condition, which can develop without warning after stem-cell transplantation and can progress rapidly causing severe kidney or lung dysfunction and lead to multi-organ failure,” said Paul G. Richardson, MD, of the Dana-Farber Cancer Institute in Boston, in a press release from the company. “Thus, it can derail a patient’s recovery from the curative intent of a stem-cell transplant, with patients who develop VOD and multi-organ failure facing an overall mortality rate of over 80%."
Defibrotide was granted priority review status and orphan drug designation, allowing for a faster approval process and incentives and fee waivers to assist in its development. The approval was based on data from a phase II trial with 75 patients, a phase III trial with 102 patients, and an expanded access trial with an additional 351 patients.
All patients in the trials had a diagnosis of hepatic VOD with renal or pulmonary dysfunction following HSCT. In the phase II trial, 44% of patients survived to 100 days after HSCT. In the phase III trial, this rate was 38%, and in the expanded access cohort the 100-day survival rate was 45%. The FDA noted in a press release that the expected survival rates at 100 days after HSCT would be between 21% and 31% for patients with severe hepatic VOD who did not receive defibrotide.
Safety data on the drug was based on 176 patients. The most common adverse events included hypotension, diarrhea, vomiting, nausea, and epistaxis. The most common serious adverse events included hypotension (11% of patients) and alveolar hemorrhage (7% of patients).
“The approval of Defitelio fills a significant need in the transplantation community to treat this rare but frequently fatal complication in patients who receive chemotherapy and HSCT,” said Richard Pazdur, MD, director of the FDA’s Office of Hematology and Oncology Products, in a press release.