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

Approved TTR Stabilizer Therapies Beyond Tafamidis

Tafamidis is currently the only FDA-approved TTR stabilizer therapy for transthyretin amyloid cardiomyopathy (ATTR-CM). There are no other approved TTR stabilizer therapies besides tafamidis (available as Vyndaqel and Vyndamax) for the treatment of ATTR-CM.

Available TTR-Targeting Therapies

FDA-Approved TTR Stabilizers:

• Tafamidis (Vyndaqel/Vyndamax): The only approved TTR stabilizer for ATTR-CM
  • Available in two formulations:
    • Tafamidis meglumine 20 mg capsules (recommended dose: 80 mg/day)
    • Tafamidis 61 mg capsules (recommended dose: 61 mg/day)
  • Indicated for both wild-type and hereditary ATTR-CM 1, 2
  • Reduces cardiovascular mortality and cardiovascular-related hospitalization in NYHA class I-III patients 1

Other TTR-Targeting Therapies (Not TTR Stabilizers):

1. TTR Silencers (for ATTRv with polyneuropathy only):

   • Inotersen
   • Patisiran
   • Vutrisiran
   • These are approved only for ATTRv with polyneuropathy, not for ATTR-CM 1

2. Other Potential TTR Stabilizers (not FDA-approved for ATTR-CM):

   • Diflunisal (an NSAID with TTR stabilizing properties)
     • Not FDA-approved for ATTR-CM
     • Limited evidence of benefit on surrogate endpoints 1
     • Not recommended for patients with significant kidney impairment (eGFR <45 mL/min/1.73 m²) 1

3. TTR Disruptors (experimental, not approved):

   • Doxycycline plus tauroursodeoxycholic acid (TUDCA)
   • Epigallocatechin-3-gallate (EGCG) from green tea
   • Limited evidence on surrogate endpoints, no proven impact on mortality or morbidity 1

Clinical Considerations

• Tafamidis has demonstrated significant clinical benefits in ATTR-CM:

  • 30% reduction in all-cause mortality
  • Reduced cardiovascular-related hospitalizations
  • Slowed decline in functional capacity 3, 4

• Tafamidis is generally well-tolerated with a safety profile similar to placebo 3

• Key limitations:

  • High cost (>$225,000 annually) with low economic value (>$180,000 per QALY gained) 1
  • Less benefit observed in NYHA class III patients and no proven benefit in NYHA class IV 1
  • Not studied in patients with severe aortic stenosis or impaired renal function (eGFR <25 mL/min/1.73 m²) 1

Important Clinical Pitfalls

1. Ensure proper diagnosis of ATTR-CM before initiating therapy:

   • Genetic testing to differentiate ATTRwt from ATTRv
   • Rule out AL amyloidosis with serum free light chain assay and immunofixation electrophoresis

2. Tafamidis prevents but does not reverse amyloid deposition, so early treatment is crucial for maximum benefit 1

3. Standard heart failure medications may be poorly tolerated in ATTR-CM:

   • ARNi, ACEi, and ARBs may worsen hypotension
   • Beta blockers may worsen symptoms as patients rely on heart rate response 1

4. All patients with cardiac amyloidosis and atrial fibrillation should receive anticoagulation regardless of CHA₂DS₂-VASc score 1