Are there any other approved Transthyretin (TTR) stabilizer therapies besides tafamidis (Tafamidis)?

Approved TTR Stabilizer Therapies Beyond Tafamidis

Currently, tafamidis is the only FDA-approved TTR stabilizer for ATTR cardiomyopathy, while other disease-modifying therapies target different mechanisms or are approved only for specific ATTR variants with polyneuropathy. 1

Current Approved TTR-Targeting Therapies

TTR Stabilizers

• Tafamidis: FDA-approved for both wild-type and variant ATTR cardiomyopathy (ATTR-CM)
  • Available in two formulations: tafamidis meglumine 80mg (4×20mg capsules) or tafamidis 61mg once daily 1
  • Significantly reduces cardiovascular mortality and hospitalization in NYHA class I-III patients 1

TTR Silencers (RNA-targeting therapies)

• Patisiran: FDA-approved only for ATTRv with polyneuropathy, not cardiomyopathy 1
• Inotersen: FDA-approved only for ATTRv with polyneuropathy, not cardiomyopathy 1
• Vutrisiran: FDA-approved only for ATTRv with polyneuropathy, not cardiomyopathy 1

Other Potential TTR-Targeting Agents (Not FDA-Approved for ATTR-CM)

Other TTR Stabilizers

• Diflunisal: An NSAID with TTR-stabilizing properties
  • Not FDA-approved for ATTR-CM
  • Has shown limited benefit on surrogate endpoints like LV mass 1
  • Not recommended for patients with significant kidney impairment (eGFR <45 mL/min/1.73 m²) or volume overload due to potential adverse renal effects 1

TTR Disruptors (Investigational)

• Doxycycline with tauroursodeoxycholic acid (TUDCA): Limited benefit on surrogate endpoints 1
• Epigallocatechin-3-gallate (EGCG) (in green tea): Limited benefit on surrogate endpoints 1

Important Clinical Considerations

• Mechanism differences: TTR stabilizers (tafamidis, diflunisal) prevent TTR misfolding, while TTR silencers (patisiran, inotersen, vutrisiran) reduce TTR production through mRNA inhibition 1

• Treatment selection: Based on ATTR subtype (wild-type vs. variant) and presence of cardiac or neurological manifestations 1

• Monitoring requirements:

  • Inotersen requires weekly platelet monitoring and biweekly kidney function monitoring due to risks of thrombocytopenia and glomerulonephritis 1
  • Tafamidis has minimal monitoring requirements with a safety profile similar to placebo 2

• Cost considerations: Tafamidis provides low economic value at 2020 list prices (>$180,000 per QALY gained) 1

Key Pitfalls to Avoid

• Avoid assuming all TTR-targeting therapies are interchangeable: The FDA approvals are specific to disease manifestations (cardiomyopathy vs. polyneuropathy) and ATTR subtypes (wild-type vs. variant)

• Avoid delaying treatment: Since tafamidis prevents but doesn't reverse amyloid deposition, earlier treatment in the disease course is expected to provide greater benefit 1

• Avoid inappropriate use of TTR silencers: While patisiran and inotersen are effective for polyneuropathy in ATTRv, they are not currently approved for ATTR-CM 1

In summary, tafamidis remains the only FDA-approved TTR stabilizer specifically for ATTR cardiomyopathy. Other disease-modifying therapies target different mechanisms or are approved only for specific ATTR variants with polyneuropathy.