ASPAVELI (pegcetacoplan) - Paroxysmal nocturnal haemoglobinuria (PNH)

The clinical benefit of ASPAVELI (pegcetacoplan) 1,080 mg solution for infusion 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:

• demonstration of the superiority of ASPAVELI (pegcetacoplan) compared to the continuation of eculizumab in terms of the improvement in haemoglobin levels after 16 weeks in patients with haemoglobin levels <10.5 g/dL after treatment with a stable dose of eculizumab for at least the previous 3 months,
• the substantial effect size demonstrated for this relevant endpoint, with a difference of +3.84 g/dL in favour of pegcetacoplan,

and despite:

• the absence of any available superiority analysis with respect to the need for transfusions given the discontinuation of the ranked analysis before this endpoint, with only non-inferiority having been demonstrated for this endpoint,
• the absence of long-term comparative data, in particular enabling assessment of the impact of pegcetacoplan in comparison with eculizumab on the occurrence of thrombotic events, the leading cause of death in these patients,
• the more frequent occurrence of serious haemolysis (4.9% versus 2.6% during the randomised period) or haemolysis having led to treatment discontinuation (7.3% versus 0) in the pegcetacoplan group after switching from eculizumab to pegcetacoplan,
• the lack of evidence of a benefit on patients’ quality of life,

the Committee deems that ASPAVELI (pegcetacoplan) 1,080 mg solution for infusion 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 FABHALTA (iptacopan) and VOYDEYA (danicopan).

In the other situations of the MA: not applicable.