Can Amvuttra Remove Existing Amyloid Deposits in hATTR Patients?
No, vutrisiran (Amvuttra) cannot remove existing amyloid deposits—it works by preventing new amyloid formation through TTR gene silencing, which reduces serum TTR protein by approximately 83%, but does not clear pre-existing tissue deposits. 1
Mechanism of Action and Tissue Effects
Vutrisiran causes degradation of both mutant and wild-type TTR mRNA through RNA interference, which results in reduction of serum TTR protein and slows further TTR protein deposits in tissues—but this mechanism does not actively remove amyloid that has already accumulated 1
The drug distributes primarily to the liver after subcutaneous dosing, where it is metabolized by endo- and exonucleases, targeting the source of TTR production rather than existing deposits 1
Clinical Evidence on Disease Progression
Vutrisiran slows but does not halt amyloid deposition, and the disease remains progressive despite treatment 2
In the HELIOS-A trial, vutrisiran significantly reduced neuropathy impairment and improved quality of life measures compared to placebo, demonstrating disease stabilization rather than reversal 3, 4
The American College of Cardiology emphasizes that vutrisiran preserves function and slows decline rather than preventing all future symptoms indefinitely 2
Contrast with AL Amyloidosis
In AL amyloidosis (a different disease), eradication of amyloidogenic light chains with anti-plasma cell therapy can lead to improvement in organ manifestations, with proteinuria decreasing progressively over months to years—however, this mechanism does not apply to ATTR amyloidosis 5
Even in AL amyloidosis where the source is eliminated, amyloid persists in tissue on biopsy, making it impossible to distinguish new deposits from pre-existing ones 5
Treatment Expectations and Timing
Early treatment with vutrisiran produces superior outcomes compared to delayed therapy, with better neuropathy impairment scores and quality of life measures, because it prevents accumulation of additional deposits before irreversible organ damage occurs 2
The American College of Cardiology recommends initiating vutrisiran immediately upon detection of polyneuropathy or cardiac involvement, as earlier treatment yields better functional outcomes by limiting total amyloid burden 2
Symptomatic management remains necessary alongside disease-modifying therapy for neuropathic pain, autonomic dysfunction, and cardiac symptoms, as existing deposits continue to cause symptoms 2
Important Clinical Considerations
Vitamin A supplementation (3,000 IU daily) is required with vutrisiran due to reduced retinol transport, as the drug reduces mean steady state serum vitamin A by 62% over 9 months 2, 1
Treatment should demonstrate a beneficial response compared to baseline—patients showing disease progression despite therapy may require reassessment of treatment strategy 6
A kidney biopsy in ATTR patients is usually not helpful for assessing treatment response because amyloid persists in tissue regardless of whether new deposition is occurring 5