Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication DEFITELIO is indicated for the treatment of adult and pediatric patients with hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), with renal or pulmonary dysfunction following hematopoietic stem-cell transplantation (HSCT). FDA label
Also known as defitelio
Defibrotide · 6 trials · 9 indications
VOD-free survival is a composite of survival status and VOD occurrence as determined by modified Seattle criteria adjudicated by a blinded independent EPAC. An event is defined as a VOD diagnosis (as assessed by the EPAC) or death, whichever, is earlier, up to and including Day +30 post-HSCT. The values reported below are participants who did not experience VOD or death by Day +30 post-HSCT.
The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.
The 95.1% CI instead of 95% CI is used for the final analysis to provide a small adjustment for the fact that an interim analysis was performed.
Cumulative Incidence Percentage of Grade B to D aGvHD was defined using the International Bone Marrow Transplant Registry (IBMTR) Severity Index. Grade B is defined as Skin stage = 2 or Liver stage = 1 to 2 or GI stage = 1 to 2. Grade C is defined as Skin stage = 3 or Liver stage = 3 or GI stage = 3. Grade D is defined as a Skin stage = 4 or Liver stage = 4 or GI stage = 4.
Major hemorrhagic complications will be based on the International Society on Thrombosis and Haemostasis Bleeding scale. 1. Fatal Bleeding, and/or 2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome, and/or 3. Bleeding associated with a decline in hemoglobin level of \> 2.0 g/dl, leading to transfusion of two or more units of whole blood or red cells. 4. In addition, symptomatic alveolar hemorrhage, macroscopic hematuria, uncontrolled menorrhagia or epistaxis or bleeding from any wound site would also be considered a major hemorrhagic event.
| Arm | Type | Description |
|---|---|---|
| Defibrotide | EXPERIMENTAL | Defibrotide is administered intravenously at a dose of 25 mg/kg/day in addition to best supportive care on the day before the first day of the conditioning regimen and will continue (for those patients without a VOD diagnosis) for a recommended minimum of 21 days and end no later than Day +30 post HSCT |
| Best Supportive Care | OTHER | Best supportive care alone (without the addition of defibrotide) according to institutional guidelines and patient need, is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner, or diagnosis of VOD, if applicable |
| Historical Control | NO_INTERVENTION | Historical control group |
| Arm A Lower dose | EXPERIMENTAL | This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide. \- Arm I: On days 2-14, patients receive a lower dose of defibrotide IV over 2 hours every 6 hours. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity |
| Arm B Higher Dose | EXPERIMENTAL | This is a randomized, multicenter study. All patients initially receive the same dose of defibrotide IV over 2 hours every 6 hours on day 1. On day 2, patients are randomized to 1 of 2 doses of defibrotide. \- Arm II: On days 2-14, patients receive a higher dose of defibrotide IV over 2 hours every 6 hours. In both arms, courses repeat every 14 days in the absence of disease progression or unacceptable toxicity |
| Defibrotide Prophylaxis | EXPERIMENTAL | Standard of Care Immunoprophylaxis + Defibrotide |
| Standard of Care | ACTIVE_COMPARATOR | Standard of Care Immunoprophylaxis Alone |
| Name | Type | Description |
|---|---|---|
| Defibrotide | DRUG | - |
| Best Supportive Care | OTHER | - |
| Standard of Care | DRUG | Administered according to local institutional guidelines, physician preference, and patient need. |
Inclusion Criteria: 1. Patient must be above the age of 1 month as of the start date of study treatment. 2. Patient must be scheduled to undergo allogeneic hematopoietic stem cell transplant (HSCT) (adults or pediatric patients) or autologous HSCT (pediatric patients only) and be at high risk or ve...
Defibrotide is used for hepatic veno-occlusive disease, also called veno-occlusive disease, including severe hepatic veno-occlusive disease. It has also been studied in graft-versus-host disease and in COVID-19 acute respiratory distress syndrome. Jazz Pharmaceuticals plc develops the drug.
Defibrotide targets ADORA2B, ADORA2A, ADORA1, F2, and PLG. It acts as an agonist at these targets. This small molecule interacts with adenosine receptor subtypes and with factors involved in coagulation and fibrinolysis.
Jazz Pharmaceuticals plc makes Defibrotide. The company trades on the Nasdaq under the ticker JAZZ. Jazz Pharmaceuticals is the developer of the asset across its studied indications, which include hepatic veno-occlusive disease, graft-versus-host disease, and COVID-19.
Defibrotide is in Phase 1 development according to the current pipeline listing, and it remains an investigational drug. Completed studies include a Phase 1 COVID-19 ARDS trial, a Phase 2 acute graft-versus-host disease trial, and Phase 3 hepatic veno-occlusive disease trials.
Defibrotide has been studied in NCT04530604, a Phase 1 trial in SARS-CoV2 COVID-19 acute respiratory distress syndrome, and NCT03339297, a Phase 2 open-label study for prevention of acute graft-versus-host disease. Phase 3 trials include NCT02851407 and NCT00628498 in hepatic veno-occlusive disease.
Defibrotide trials have enrolled 1,206 patients in total across the listed studies. The largest was NCT00628498, a Phase 3 treatment IND study in hepatic veno-occlusive disease with 1,206 patients. NCT02851407 enrolled 372 patients and NCT03339297 enrolled 152 patients.