DEFITELIO 80 mg/ml (défibrotide)

Key points

Favourable opinion for maintenance of reimbursement in the treatment of severe hepatic veno-occlusive disease (VOD) also known as sinusoidal obstruction syndrome (SOS) in haematopoietic stem-cell transplantation (HSCT) therapy.

What therapeutic improvement?

Therapeutic improvement in the management of the condition.

Role in the care pathway?

The prevention of VOC is primarily related to reducing the intensity of myelosuppressive chemotherapy conditioning before haematopoietic stem-cell transplantation. In recent years, the incidence of the occurrence of hepatic VOD has decreased thanks to changes in its management: patients at high risk are identified, low-intensity conditioning is favoured, cyclophosphamide-free chemotherapy protocols have been introduced, norethisterone-based treatments are no longer used, the concomitant administration of hepatotoxic drugs is avoided, patients are given transplants sooner, the general condition of patients at the time of transplantation is better.

DEFITELIO (defibrotide) is the only curative treatment for hepatic VOD to be approved in the USA and Europe. European Society for Blood and Marrow Transplantation (EBMT) guidelines recommend the use of DEFITELIO (defibrotide) as a treatment for hepatic VOD. In addition, other proprietary medicinal products are used off-label in this indication: recombinant plasminogen activator factor (ACTILYSE), N-acetylcysteine, methylprednisolone. A transjugular intrahepatic shunt may also be created in certain cases. In its opinion of July 2014, the Committee had considered that DEFITELIO (defibrotide) is a first-line treatment for severe hepatic VOD in adults, adolescents, children and infants over one month of age.

To date, DEFITELIO (defibrotide) does not have an MA as prophylactic therapy in adults at risk of developing VOD or in children. It should be noted that a phase 3, randomised, open-label study aimed at comparing DEFITELIO (defibrotide) as prophylaxis for VOD versus the standard of care in adults and children at high or very high risk of developing VOD was stopped for futility after having concluded that it was unlikely that a statistically significant difference would be attained in the final analysis of the primary endpoint (VOD-free survival at D+30 post-HSCT).

Role of the medicinal product in the care pathway:

DEFITELIO (defibrotide) remains a first-line treatment for severe hepatic VOD in adults, adolescents, children and infants over one month of age.

In the French observational study put in place at the request of the Committee following the assessment of 9 July 2014, the off-label use of DEFITELIO (defibrotide) was identified in 70% of cases, particularly in the prophylaxis of VOD. Consequently, the Committee reiterates that, with the aim of ensuring good practice, the use of DEFITELIO (defibrotide) as prophylaxis of VOD is not validated by the MA and DEFITELIO (defibrotide) should be reserved for the treatment of severe hepatic VOD, in accordance with the MA indication.