80 mg tafamidis reduces mortality compared to 20 mg in ATTR-CM patients
Tafamidis 80 mg demonstrates a significant survival benefit over tafamidis 20 mg in patients with transthyretin amyloid cardiomyopathy
HFA Discoveries 2020 webinar presented by Thibaud Damy (Creteil, France)
Introduction and methods
In the ATTR-ACT trial (Tafamidis in Transthyretin Cardiomyopathy), treatment with tafamidis meglumine resulted in a reduction in mortality and CV-related hospitalization compared to placebo in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This was in a primary comparison of pooled doses of 20 mg and 80 mg tafamidis. The trial was not designed for a definitive dose assessment. Patients who completed the ATTR-ACT trial were eligible to enroll in a long-term extension study (LTE).
This study evaluated the effect of tafamidis 80 mg compared to tafamidis 20 mg on mortality using data from the ATTR-ACT trial and the LTE study. Association were corrected for the following prognostic factors of survival: age, NT-proBNP, and functional capacity, measured by 6-minute walk test distance (6MWT).
In ATTR-ACT, 441 patients were randomized to 80 mg tafamidis, 20 mg tafamidis or placebo in a 2:1:2 ratio. After 30 months, patients in the LTE study who were on 80 mg tafamidis continued their treatment, as well as patients on 20 mg tafamidis. Patients on placebo were re-randomized in a 2:1 fashion to 80 mg tafamidis or 20 mg tafamidis. On July 2018 there was a protocol amendment to transition all LTE study participant to a new formulation of tafamidis free acid 61 mg, which is bioequivalent to tafamidis meglumine 80 mg.
- Compared to patients on 20 mg tafamidis, more patients on 80 mg tafamidis had worse NYHA class, patients on 80 mg tafamidis were older with higher NT-proBNP levels and 6 min walk test distance was shorter.
- There was no difference in mortality between the 2 dose groups after 30 months and 39 months.
- After a median follow-up of 51 months (which included patients transitioned to tafamidis free acid), 80 mg tafamidis resulted in improved survival compared to 20 mg tafamidis (unadj HR 0.7, 95%CI: 0.50-0.98, P=0.037, HR adjusted for age, NT-proBNP and 6MWT 0.571, 95%CI: 0.395-0.827, P=-0.003).
- There was no difference between the two dose groups in serious or severe treatment-emergent adverse events (TEAEs).
Benefit of 80 mg tafamidis over 20 mg was evident after longer follow-up, with significant reduction in mortality after 51 months in patients with ATTR-CM. The authors of the study concluded that these findings contribute to the evidence that tafamidis 80 mg is the preferred dose in patients with ATTR-CM.
- Our reporting is based on the information provided at HFA Discoveries -