FABHALTA (iptacopan) - Paroxysmal nocturnal haemoglobinuria (PNH)

The Committee deems that the clinical benefit of FABHALTA 200 mg (iptacopan) hard capsules is substantial only in “the treatment of adult patients with PNH who have symptomatic haemolytic anaemia after treatment with a C5 inhibitor for at least 6 months”.

Considering:

• evidence of the superiority of iptacopan versus continuation of a C5 inhibitor (ravulizumab or eculizumab) after 24 weeks of treatment, in terms of increase in haemoglobin levels, reduction in transfusion needs and reduction in episodes of haemolysis, in adult patients with PNH who have residual haemolytic anaemia after treatment with a C5 inhibitor for at least 6 months,
• the clinical relevance of these endpoints and the high effect size observed for haemoglobin levels and transfusion needs, which seems more modest for reduction of episodes of haemolysis (annualised rate of clinical breakthrough haemolysis of 0.07 versus 0.67) in a context where the history of episodes was not known,

and despite:

• a possible overestimation of the benefit observed, as it cannot be ruled out that some patients in the control group were not receiving optimised treatment with a C5 inhibitor in accordance with French practice,
• the absence of comparative data beyond 24 weeks in a context of chronic disease with potentially lifelong treatment, in order to be able to assess maintenance of the benefits and safety profile of iptacopan in the long term, along with its impact on the incidence of thrombotic events, the leading cause of death in patients,
• the absence of a demonstrated benefit on patients’ quality of life,
• the absence of robust comparative data versus pegcetacoplan, a treatment already available as second-line therapy after a C5 inhibitor, in particular the absence of a direct comparison, which would nonetheless have been justified on the date of the present assessment given their concomitant development; to date, it cannot be assumed that there is a lower risk of serious haemolysis with iptacopan than with pegcetacoplan, in view of their similar mechanisms of action,

the Committee deems that FABHALTA 200 mg (iptacopan) hard capsules provides a moderate clinical added value (CAV III) in the treatment of adult patients with PNH who have symptomatic haemolytic anaemia after treatment with a C5 inhibitor for at least 6 months, in the same way as ASPAVELI (pegcetacoplan).