ZILBRYSQ (zilucoplan) - Myasthenia

The Committee deems that the clinical benefit of ZILBRYSQ (zilucoplan) issubstantial only as an add-on to standard therapy, including first-line immuno-suppressants, for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive, who remain symptomatic.

Considering:

• evidence of the superiority of zilucoplan compared to placebo:
  • in terms of the change from baseline to week 12 in MG-ADL score (primary endpoint), with a mean change (SD) of -2.09 (0.58) points (95% CI [-3.24; -0.95]); (p<0.001),
  • on the clinical ranked secondary endpoints of disease severity assessed at week 12 (QMG and MGC scores and percentage of clinical responders),
  • in terms of quality of life measured using the specific MG-QOL15r scale, with a
    difference in mean change of -2.5 points (95% CI [-4.45; -0.54], p=0.013) out of
    30 points,

but in view of:

• comparative efficacy data limited to the short term (12 weeks),
• the safety profile reported in the studies, consistent with that of other C5 complement inhibitors, and with uncertainties in the long term,
• the lack of comparison versus rituximab or eculizumab despite the fact that this would have been possible; as well as the absence of comparison versus efgartigimod alfa or ravulizumab due to their concomitant development,

the Committee deems that, like ULTOMIRIS (ravulizumab) and VYVGART (efgartigimod alfa), ZILBRYSQ 40 mg/mL (zilucoplan) solution for injection in pre-filled syringe, as an add-on to standard therapy, including first-line immunosuppressants, provides a minor clinical added value (CAV IV) in the care pathway for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive, who remain symptomatic, excluding rituximab and SOLIRIS [eculizumab].