WAINZUA (eplontersen) - Hereditary transthyretin-mediated

The clinical benefit of WAINZUA 45 mg (eplontersen) solution for injection in pre-filled pen is moderate in the MA indication.

Considering:

• evidence of the superiority of eplontersen versus placebo in NEURO-TTRansform, a randomised, open-label phase 3 trial, for the change in serum TTR concentration and the change in mNIS+7 score,
• evidence of an improvement in quality of life, assessed by the Norfolk QOL-DN, quality of life score, as a co-primary endpoint in the NEURO-TTRansform study,
• the design of the study and its methodological limitations, i.e. an indirect comparison of the eplontersen group with an external historic placebo group from the Neuro-TTR study, which was the pivotal study for inotersen [TEGSEDI], which reduces the scope of the efficacy results observed,
• the absence of any available comparison versus a clinically relevant comparator, despite the fact that a direct comparison versus ONPATTRO (patisiran), TEGSEDI (inotersen) or VYNDAQEL (tafamidis) or a methodologically robust indirect study versus AMVUTTRA (vutrisiran) could have been feasible,
• the limited duration of the study, of 18 months, which is insufficient to guarantee maintenance of efficacy in this chronic disease.
• the safety profile of eplontersen that seems to be favourable, with follow-up limited to 18 months,

the Committee deems that WAINZUA 45 mg (eplontersen) solution for injection in pre-filled pen provides no clinical added value (CAV V) in the current care pathway, which includes therelevant comparators.