From the Guidelines
Tafamidis is currently the only FDA-approved TTR stabilizer therapy, but diflunisal is used off-label as a TTR stabilizer at a dose of 250 mg twice daily, and AG10 (acoramidis) is another TTR stabilizer in late-stage clinical development. According to the 2022 AHA/ACC/HFSA guideline for the management of heart failure 1, tafamidis is the only therapy to improve cardiovascular outcomes in ATTR-CM. However, diflunisal has been demonstrated to be effective in slowing disease progression in ATTRv polyneuropathy, although it is not FDA-approved for this indication 1.
Key Points
- Tafamidis is the only FDA-approved TTR stabilizer specifically for ATTR-CM, with a recommended dose of 80 mg once daily 1.
- Diflunisal is used off-label as a TTR stabilizer, with a dose of 250 mg twice daily, and may provide an alternative option for patients who cannot access or afford tafamidis.
- AG10 (acoramidis) is another TTR stabilizer currently in late-stage clinical development.
- Treatment with TTR stabilizers is typically long-term, as these medications slow disease progression rather than reverse existing damage.
- The choice of TTR stabilizer therapy should be individualized based on patient-specific factors, including disease severity, comorbidities, and access to treatment.
Considerations
- The cost-effectiveness of tafamidis compared to no amyloidosis-specific therapy has been evaluated in model-based analyses, with estimates suggesting that tafamidis increases average survival by 1.97 years and QALY by 1.29 1.
- However, the cost of tafamidis is high, with an annual cost of $225,000, and the incremental cost-effectiveness ratio is >$180,000 per QALY gained 1.
- Diflunisal may provide a more affordable alternative for patients who cannot access or afford tafamidis, although its use is off-label and not FDA-approved for ATTR-CM or ATTRv polyneuropathy.
From the FDA Drug Label
VYNDAQEL and VYNDAMAX are transthyretin stabilizers indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. (1)
The FDA drug label does not answer the question about other approved TTR stabilizer therapies, as it only mentions VYNDAQEL and VYNDAMAX, which are both tafamidis products, without comparing or referencing other approved TTR stabilizers.
From the Research
TTR Stabilizer Therapies
- Tafamidis is a well-established TTR stabilizer therapy, approved for the treatment of transthyretin-related amyloidosis (ATTR) in several countries 2, 3, 4, 5.
- It has been shown to slow disease progression, improve quality of life, and reduce mortality in patients with ATTR 3, 4, 5.
- In addition to tafamidis, other TTR stabilizer therapies include diflunisal, which has been suggested to stabilize TTR tetramers and may be effective in treating ATTR amyloidosis 6.
Other Approved Therapies
- There are no other approved TTR stabilizer therapies mentioned in the provided studies, aside from tafamidis and the potential use of diflunisal.
- However, other disease-modifying therapies, such as small interfering RNA (patisiran) and antisense oligonucleotide (inotersen) therapies, have demonstrated efficacy in treating ATTR amyloidosis 6.
Ongoing Research and Development
- Further research is needed to fully understand the clinical spectrum, pathogenesis, and disease-modifying therapies for transthyretin amyloidosis 6.
- The development of new therapies, including TTR stabilizers and gene-silencing agents, may provide additional treatment options for patients with ATTR amyloidosis 6.