Approval of VYNDAMAX was based on ATTR-ACT, a phase 3, multicenter, international, randomized, double-blind, placebo-controlled study, which evaluated pooled VYNDAQEL® (tafamidis meglumine) doses of 20 mg and 80 mg in 441 patients with wild-type or hereditary transthyretin cardiac amyloidosis*—a single VYNDAMAX 61-mg capsule is bioequivalent† to VYNDAQEL 80 mg (four 20-mg capsules) and is not interchangeable on a per-mg basis.1-3
5-year data
Real-world evidence
Tab Number 3
Tab Number 4
Tab Number 5
The long-term extension, post hoc, interim analysis compared patients who first received1:
- VYNDAQEL 80 mg, continuing with VYNDAQEL 80 mg, then transitioned to VYNDAMAX (continuous VYNDAQEL/VYNDAMAX)
- Placebo who were randomized (2:1) to VYNDAQEL 80 mg or 20 mg,|| then transitioned to VYNDAMAX (placebo to VYNDAQEL/VYNDAMAX)
- The VYNDAQEL 20-mg arm in ATTR-ACT was not included in this analysis
The data reported on the long-term efficacy and safety of tafamidis are from the long-term extension to the ATTR-ACT trial and are not included in the VYNDAQEL/VYNDAMAX prescribing information.
- The updated analysis with long-term survival was not prespecified. No formal hypothesis testing was performed given that the overall survival endpoint was met in ATTR-ACT study. This analysis of the long-term extension was not powered to make conclusions on all-cause mortality at 5 years
- The preliminary 5-year survival rate in this interim analysis was 53% with continuous VYNDAQEL/VYNDAMAX treatment vs 32% in the placebo-to-VYNDAQEL/VYNDAMAX group1
- No new safety concerns were observed in patients treated with VYNDAQEL or VYNDAMAX in this analysis. Incidence and types of adverse events were similar to, or lower than, those with pooled VYNDAQEL (80 mg and 20 mg) or placebo in ATTR-ACT1
- The median follow-up was 58.5 months (continuous tafamidis group) and 57.1 months (placebo-to-tafamidis group)1
Adapted from Elliott P, et al. Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy. Circ Heart Fail. 2022;15(1):e008193.
Tab Number 1
RCTs & RWE
THAOS registry
Study design
THAOS data
| RCTs | RWE |
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| RCTs |
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| RWE |
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- The Transthyretin Amyloidosis Outcomes Survey (THAOS) is a global, longitudinal, observational phase 4 study of 6718 people with ATTR cardiac amyloidosis or who are asymptomatic carriers for TTR mutations4
- The data reported on the long-term efficacy and safety of tafamidis from the long-term extension to the ATTR-ACT trial and THAOS are not included in the VYNDAQEL/VYNDAMAX prescribing information
Largest registry of patients with ATTR-CM4
33 trial sites across the US6
Characterizes the natural history of ATTR-CM across a heterogeneous patient population4
Includes patients more aligned to a contemporary|| patient population, accounting for the realities of clinical practice4
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Largest registry of patients with ATTR-CM4 |
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33 trial sites across the US6 |
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Characterizes the natural history of ATTR-CM across a heterogeneous patient population4 |
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Includes patients more aligned to a contemporary|| patient population, accounting for the realities of clinical practice4 |
To date, real-world evidence on survival in patients with ATTR-CM following tafamidis treatment has not been extensively reported.
- Post hoc analysis of patients in the THAOS registry with predominantly cardiac phenotype (N=1441)4
- Patients had a diagnosis of ATTR-CM without signs and symptoms suggestive of associated ATTR cardiac amyloidosis–related neuropathy4
- Included patients from 18 countries4
- Patients were either treatment naïve or receiving VYNDAQEL/VYNDAMAX4
- This study is an observational registry in which data were not always complete, and baseline data were not available for all patients4
- The observational nature of this study had the potential to introduce bias (eg, selection, ascertainment, temporal bias)4||
- Median follow-up time was 2 years in both groups, limiting the reliability of the survival analyses in later months4
- Data on the use of SPECT imaging in patients diagnosed with scintigraphy are not available, so misdiagnosis is possible, as scintigraphy in the absence of SPECT can lead to false positives4
Baseline characteristics
Survival rates in VYNDAQEL/VYNDAMAX-treated and untreated patients at 30 and 42 months5
- Observational retrospective analyses are designed to evaluate associations among variables, cannot establish causality between treatment and outcomes, and may introduce bias. Results are not intended to be compared with clinical trials and should be interpreted with caution in the context of the totality of the evidence4
- The tafamidis-treated group received either VYNDAQEL 80 mg or VYNDAMAX 61 mg over the full course of the THAOS study; the untreated group did not receive tafamidis during the study5
- No new safety signals were identified, supporting the long-term safety and tolerability profile of VYNDAQEL/VYNDAMAX in a real-world setting4
- Median follow-up time was ~2 years in both groups4
See the 5-year data