HEMLIBRA (emicizumab) - Haemophilia A (congenital factor VIII deficiency)

Tthe Committee deems that the clinical benefit of HEMLIBRA 30 mg/ml and 150 mg/ml (emicizumab) solution for injection is substantial in the MA indication “prophylaxis of bleeding episodes in patients with haemophilia A (congenital factor VIII deficiency), without factor VIII inhibitors who have moderate disease (FVIII ≥ 1% and ≤ 5%) with severe bleeding phenotype”.

Considering:

• the efficacy of HEMLIBRA (emicizumab) observed in long-term prophylaxis in patients with moderate haemophilia A in the HAVEN 6 clinical study, in which the primary endpoint was assessment of safety, with an annualised bleeding rate (primary efficacy endpoint) estimated at 0.9 (CI95%, 0.50-1.78) with 68.6% of patients having had no treated bleeds,
• the low quality of this evidence given the study’s major methodological limitations, in particular its open-label nature, with no control of sources of bias for estimation of the treated bleed rate, the purely descriptive nature of the results in the absence of any hypothesis with respect to the expected effect of emicizumab, and the small patient sample on which the assessment was based (data from a subgroup of 51 patients),
• uncertainties with respect to the representativity of the population included compared to that validated by the MA “patients with haemophilia A without factor VIII inhibitors, who have moderate disease with severe bleeding phenotype”, given the high level of heterogeneity of the patients included, particularly in terms of bleeding profile, and the fact that the endogenous FVIII levels at the time of inclusion were not known for all these patients, which may have led to underestimation of the number of patients included with mild
  haemophilia,
• the absence of robust data enabling assessment of the benefit of prophylaxis with
  emicizumab in comparison with conventional factor VIII prophylaxis,

and despite:

• the expected benefit on quality of life due to the reduced burden of prophylactic treatment compared to FVIIl,

The Committee deems that HEMLIBRA 30 mg/ml and 150 mg/ml (emicizumab) solution for injection provides no clinical added value (CAV V) in the current care pathway.