CEVENFACTA (eptacog bêta - FVIIa) - Hémophilie congénitale

Key points

Disapproval of reimbursement for the marketing authorisation indication:

“CEVENFACTA is indicated for adult and adolescent patients (aged 12 years and over) for the treatment of bleeding episodes and for the prevention of bleeds occurring during surgery or invasive procedures in the following patient cohorts:

• High-responder patients with congenital haemophilia with high-titre clotting factor VIII or IX inhibitors (i.e. titre ≥5 Bethesda units (BU));

Patients with congenital haemophilia with low-titre inhibitors (BU <5), but for whom a strong response to the administration of factor VIII or factor IX is expected, or who may be refractory to increasing the FVIII or FIX dose”.

Role in therapeutic strategy?

Timely control of spontaneous or trauma-induced bleeding events is key in delaying and/or preventing irreversible tissue and joint damage.

For haemophilia patients with inhibitors, the therapeutic options available to treat bleeds or prevent them from occurring during surgery are limited. They essentially consist of “bypass” agents:

• rFVIIa (NOVOSEVEN) and CCPa (FEIBA). The rFVIIa available, NOVOSEVEN, can be used as a first-line treatment in these contexts.
• the use of CCPa (FEIBA) is limited, in accordance with its marketing authorisation, to haemophilia A and B patients exhibiting high-responder inhibitors, as a first-line treatment for haemophilia A, and only in the event of failure to respond to rFVIIa for haemophilia B patients (risk of anamnestic boost of inhibitors).

Note that the availability in 2019 of emicizumab (HEMLIBRA), a medicinal product indicated for the long-term prophylaxis of haemophilia A patients in the presence of anti-FVIII inhibitors, has required adaptation of the care regimen for bleeds, suspected bleeds, and for emergency or scheduled invasive procedures. This has led to the drafting of proposals, by various learned societies in consultation, in respect of the care of haemophilia A patients with inhibitors. For haemorrhagic accident treatment, tranexamic acid is proposed as a first-line treatment alone for isolated mucosal bleeding and rFVIIa for major bleeding as defined by ISTH criteria. For surgical procedures for which the bleeding risk is deemed to be minor and in the absence of any added bleeding risk, it is proposed to envisage prescribing an additional haemostatic medicinal product such as rFVIIa (NOVOSEVEN). rFVIIa is a first-line treatment for major surgical procedures and in the event of postoperative bleeding that is deemed to be abnormal in the context of minor surgery. The role of CCPa is restricted to cases of inefficacy of rFVIIa or human FVIII or where FVIII cannot be used, under strict clinical and biological medical monitoring, on account of the synergistic action and risk of thrombotic microangiopathy when CCPa and emicizumab are used concomitantly

Role of the medicinal product

Considering:

• The insufficient clinical efficacy data available to establish its efficacy in the treatment of major bleeding and in the prevention of bleeding during major surgical procedures; moreover, there are weaknesses in the evidence of its efficacy in the treatment of minor to moderate episodes,
• The need partially met by the alternatives available, in particular the rFVIIa NOVOSEVEN for which significant follow-up of use is available (used in France since 1996), and which offers the advantage of being suitable for use in children under 12 years, unlike CEVENFACTA (eptacog beta - rFVIIa) for which marketing authorisation was denied due to lack of evidence of efficacy in the PERSEPT-2 study,
• The inability, due to a lack of comparative data, to rule out a loss of chance for patients with CEVENFACTA (eptacog beta - rFVIIa) compared to the use of the rFVIIa already available (NOVOSEVEN),
• And despite an acceptable safety profile,

the Committee deems that CEVENFACTA (eptacog beta - rFVIIa) has no role in the current therapeutic strategy.