Clinical Data

STUDIES INCLUDED A BROAD RANGE OF ADULT AND PEDIATRIC PATIENTS WITH VOD WITH RENAL OR PULMONARY DYSFUNCTION FOLLOWING HSCT1
Study 1 Study 2 Study 3
Study design Prospective Prospective Expanded access study
Number of patients 102 75 351
VOD associated with: Multi-organ dysfunction (pulmonary, renal, or both)a Multi-organ dysfunction Renal or pulmonary dysfunction
Median age (years)
(range)
21
(<1, 72)
32
(<1, 61)
15
(<1, 69)
Type of transplant, n (%)
Allogeneic
Autologous
90 (88)
12 (12)
67 (89)
8 (11)
317 (90)
34 (10)
Ventilator or dialysis dependent at study entry, n (%) 34 (33) 8 (11) 149 (42)
Median number of days on treatment (days)
(range)
21.5
(1, 58)
19.5
(3, 83)
21.0b
(1, 93)
Treatment dose of Defitelio 6.25 mg/kg infusion every 6 hours

aA diagnosis of VOD was made using the following criteria: bilirubin ≥2 mg/dL and at least 2 of the following—hepatomegaly, ascites, and weight gain >5% by Day +21 post HSCT. The multi-organ dysfunction was to have occurred by Day +28 post HSCT. Patients were not permitted to receive concomitant medications such as heparin, warfarin, or alteplase because of an increased risk of bleeding.

bDuration of treatment from first dose to last dose is presented because days without treatment were not captured for the expanded access study.

DEFITELIO WAS PROVEN TO IMPROVE SURVIVAL AT DAY +100 CONSISTENTLY ACROSS 3 STUDIES1

SURVIVAL AT DAY +100 POST HSCT WITH DEFITELIO ACROSS STUDIES IN ADULT AND PEDIATRIC PATIENTS1

Survival at Day +100 post HSCT with Defitelio across studies in adult and pediatric patients

EXPECTED DAY +100 SURVIVAL

WITH SUPPORTIVE CARE

21% TO 31%

Based on published reports and analyses of patient-level data for individuals with hepatic VOD with renal or pulmonary dysfunction who received supportive care or interventions other than Defitelio.1

DELAYS IN DEFITELIO INITIATION WERE ASSOCIATED WITH INCREASED MORTALITY AT DAY +1002

Defitelio vial
IN AN EXPLORATORY POST HOC ANALYSIS FROM STUDY 31,2
  • Analysis of Study 3 indicated that increased mortality at Day +100 was associated with longer delays in Defitelio administration following a diagnosis of VOD with renal or pulmonary dysfunction (confirmed by the Cochran-Armitage trend test; P<0.001)

    — Analysis based on adult and pediatric patients (n=351) with a diagnosis of VOD with renal or pulmonary dysfunction

    — The reason for initiation delay following diagnosis was not assessed in this expanded access study

HSCT=hematopoietic stem-cell transplantation; VOD=veno-occlusive disease.

View the safety profile for Defitelio

Indication

Defitelio® (defibrotide sodium) 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).

Important Safety Information

Contraindications

Defitelio is contraindicated in the following conditions:
  • Concomitant administration with systemic anticoagulant or fibrinolytic therapy
  • Known hypersensitivity to Defitelio or to any of its excipients

Warnings and Precautions

Hemorrhage

Defitelio may increase the risk of bleeding in patients with VOD after HSCT. Do not initiate Defitelio in patients with active bleeding. Monitor patients on Defitelio for signs of bleeding. If bleeding occurs, withhold or discontinue Defitelio.

Concomitant systemic anticoagulant or fibrinolytic therapy may increase the risk of bleeding and should be discontinued prior to Defitelio treatment. Consider delaying Defitelio administration until the effects of the anticoagulant have abated.

Hypersensitivity Reactions

Hypersensitivity reactions including rash, urticaria, and angioedema have occurred in less than 2% of patients treated with Defitelio. One case of an anaphylactic reaction was reported in a patient who had previously received Defitelio. Monitor patients for hypersensitivity reactions, especially if there is a history of previous exposure. If a severe hypersensitivity reaction occurs, discontinue Defitelio, treat according to the standard of care, and monitor until symptoms resolve.

Most Common Adverse Reactions

The most common adverse reactions (incidence ≥10% and independent of causality) with Defitelio treatment were hypotension, diarrhea, vomiting, nausea, and epistaxis.

Please see full Prescribing Information.

References:
  1. Defitelio [package insert]. Palo Alto, CA: Jazz Pharmaceuticals.
  2. Richardson PG, Smith AR, Triplett BM, et al. Br J Haematol. 2017;178(1):112‐118.