ULTOMIRIS (ravulizumab)

Key points

Favourable opinion for reimbursement in the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) :

• in patients with haemolysis with clinical symptom(s) indicative of high disease activity
• in patients who are clinically stable after having been treated with eculizumab for at least the past 6 months.

What therapeutic improvement ?

Therapeutic improvement compared to eculizumab (SOLIRIS).

Role in the care pathway ?

The treatment of paroxysmal nocturnal haemoglobinuria is currently based on eculizumab (SOLIRIS), blood transfusions in the event of severe anaemia and other symptomatic treatments without a validated indication in the treatment of PNH, such as anticoagulants.

Eculizumab (SOLIRIS), a complement inhibitor, is the only medicinal treatment with a validated indication in PNH. This medicinal product is only reimbursed in adults with a history of transfusions. Although it has an MA in children and adults without a history of transfusions, eculizumab is not reimbursed in these populations, since the pharmaceutical company has not applied for its inclusion in the list.

Bone marrow transplantation is currently the only treatment that can cure PNH but is only indicated in the event of associated severe bone marrow failure or myelodysplastic syndrome due to the complexity and risks associated with this procedure.

If eculizumab treatment fails, allogeneic haematopoietic stem cell transplantation can sometimes be envisaged but these cases are very rare. In patients not eligible for transplant, management is based on transfusions alone.

Role of the medicinal product in the care pathway

ULTOMIRIS (ravulizumab) is a novel complement inhibitor that has demonstrated non-inferior efficacy to that of SOLIRIS (eculizumab) in terms of control of haemolysis and need for transfusions, both in adult patients naïve to complement inhibitor treatment and as a switch from eculizumab (SOLIRIS) in clinically stable patients treated for at least 6 months.

To date, there is no demonstrated benefit of ULTOMIRIS (ravulizumab) compared to SOLIRIS (eculizumab) in terms of efficacy and safety, particularly for the risk of thromboembolic events, a major cause of death in paroxysmal nocturnal haemoglobinuria.

This new medicinal product presents the advantage of a less frequent dosing regimen than that of SOLIRIS (eculizumab), with infusion every 8 weeks instead of every 2 weeks (minimum duration of 1.7 to 2.7 hours for ravulizumab and duration of 25 to 45 minutes for eculizumab).  An improvement in the care conditions for patients is therefore expected with ULTOMIRIS (ravulizumab) compared to SOLIRIS (eculizumab), although its benefit in terms of improving quality of life remains to be confirmed.

Considering these elements, the Committee deems that ULTOMIRIS (ravulizumab) is a first-line treatment in the management of adult patients with paroxysmal nocturnal haemoglobinuria :

• in complement inhibitor naïve patients,
• or as a switch from eculizumab (SOLIRIS) in clinically stable patients treated for at least 6 months.

The Committee reiterates that ravulizumab (ULTOMIRIS) has no marketing authorisation in patients not having responded to eculizumab.

Insofar as ULTOMIRIS (ravulizumab) is a complement protein C5 inhibitor that increases the patient’s predisposition to meningococcal infection or septicaemia due to its mechanism of action, the Transparency Committee reiterates that its prescription must be combined with vaccination against meningococcal infections using the ACYW conjugated tetravalent vaccine and the serogroup B invasive meningococcal infection vaccine, in accordance with 2020 vaccination schedule guidance[1]. In addition, and in the same way as for the complement protein C5 inhibitor SOLIRIS (eculizumab)[2], the Committee recommends prophylactic antibiotic therapy for all patients treated with ULTOMIRIS (ravulizumab).