BEYONTTRA (acoramidis) - Amyloidosis with cardiomyopathy

The clinical benefit of BEYONTTRA (acoramidis) 356 mg film-coated tablets is moderate in the treatment of wild-type or variant transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM).

Considering:

• evidence of a superiority of acoramidis compared to placebo in a phase 3 randomised, double-blind study on a composite primary endpoint that included all-cause mortality, cumulative frequency of cardiovascular-related hospitalisation, change in NT-pro BNP levels and change in 6-minute walk distance assessed at 30 months, with a pair-wise win ratio assessed at 1.77 (p<0.001),
• the effect size for the composite primary endpoint mainly driven by the change in NT-pro BNP levels, not all-cause mortality, which is regrettable,
• the absence of a significant difference versus placebo for the primary endpoint of part A assessed at 12 months, which was the change in 6-minute walk distance,
• inconsistent evidence of an improvement in terms of quality of life, measured using a specific, validated score for the disease (KCCQ-OS),
• the methodological limitations of the phase 3 study, which reduces the scope of its efficacy results, with, in particular, late modifications to the components of the primary endpoint and their hierarchy, as well as different management of missing data depending on the endpoints,
• an indirect comparative study between acoramidis and tafamidis, in the absence of possible direct comparison, suggesting a superior efficacy and better tolerance of acoramidis; the methodological limitations of this comparison, meaning that the findings are exploratory in nature,
• the safety profile of acoramidis, which appears to be favourable, with follow-up limited to 42 months (based on the ATTRibute-CM study after 30 months and the data available after 12 months in the open-label extension study),

the Committee deems that BEYONTTRA (acoramidis) provides no clinical added value (CAV V) in the current care pathway, which includes the relevant comparators.