How AMVUTTRA works

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How AMVUTTRA works
AMVUTTRA® mechanism of action
Watch this video to learn how AMVUTTRA works

See how treatment with AMVUTTRA led to a reduction in serum TTR protein.

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AMVUTTRA molecule MOA

AMVUTTRA is an RNAi therapeutic that reduces TTR protein production1

What is AMVUTTRA?

AMVUTTRA is an RNAi therapeutic indicated for the treatment of the polyneuropathy of hATTR amyloidosis in adults.1 AMVUTTRA is a double-stranded small interfering RNA (siRNA) that is formulated for targeted delivery to hepatocytes, the primary source of TTR protein production.1-3 

Choose below to see:

Effect of TTR protein misfolding
Mechanism of action for AMVUTTRA

TTR protein in a patient with hATTR amyloidosis2,3

Image of AMVUTTRA™ (vutrisiran) being delivered to hepatocytes, the primary source of TTR protein production.
Liver: Primary site of TTR production
Image of AMVUTTRA™ (vutrisiran) being delivered to hepatocytes, the primary source of TTR protein production.
Variants lead to misfolding of TTR proteins
Progressive symptoms
Image of AMVUTTRA™ (vutrisiran) being delivered to hepatocytes, the primary source of TTR protein production.
Misfolded TTR protein
forms amyloid deposits
in tissues

Reduction of amyloid deposits1,4

Image of AMVUTTRA™ (vutrisiran) being delivered to hepatocytes, the primary source of TTR protein production.
AMVUTTRA harnesses the endogenous RNAi pathway, which causes the degradation of variant and wild-type TTR mRNA1
Image of AMVUTTRA™ (vutrisiran) being delivered to hepatocytes, the primary source of TTR protein production.
This results in a reduction of serum TTR protein and TTR protein deposits in tissues1,4,5
Fewer amyloid deposits in tissues1,4
Image of AMVUTTRA™ (vutrisiran) being delivered to hepatocytes, the primary source of TTR protein production.
This results in a reduction of serum TTR protein and TTR protein deposits in tissues1,4,5

AMVUTTRA uses an Enhanced Stabilization Chemistry-GalNAc conjugate designed for high metabolic stability, resulting in increased potency and prolonged duration of activity to allow infrequent dosing.1,6

GaINAc=N-acetylgalactosamine; hATTR=hereditary transthyretin-mediated; mRNA=messenger RNA; RNA=ribonucleic acid; RNAi=RNA interference; TTR=transthyretin.

In the HELIOS-A study…

Treatment with AMVUTTRA led to rapid, powerful, and sustained reduction in serum TTR7

Percent change from baseline in serum TTR levels7,8,a
Graph showing serum TTR reduction with AMVUTTRA in the HELIOS-A study.

aBars represent SEM (standard error of the mean).

Percent change from baseline in serum TTR levels7,8,a
Graph showing serum TTR reduction with AMVUTTRA in the HELIOS-A study.

aBars represent SEM (standard error of the mean).

  • Serum TTR was evaluated in patients with hATTR amyloidosis with polyneuropathy treated with 25 mg of AMVUTTRA via subcutaneous injection once every 3 months1
  • Similar reduction in serum TTR was observed regardless of V30M variant status, previous TTR stabilizer use, sex, age, weight, or race1,7

88% mean reduction of serum TTR
with dosing once every 3 months1,7

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Important Safety Information and Indication

Important Safety Information

Reduced Serum Vitamin A Levels and Recommended Supplementation

AMVUTTRA® (vutrisiran) treatment leads to a decrease in serum vitamin A levels.

Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with AMVUTTRA, as serum vitamin A levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness).

Adverse Reactions

The most common adverse reactions that occurred in patients treated with AMVUTTRA were pain in extremity (15%), arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).

Indication

AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

For additional information about AMVUTTRA, please see the full Prescribing Information.

References

  1. AMVUTTRA Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.
  2. Holmgren G, Steen L, Ekstedt J, et al. Clin Genetics. 1991;40(3):242-246.
  3. Soprano DR, Herbert J, Soprano KJ, et al. J Biol Chem. 1985;260(21):11793-11798.
  4. Butler JS, Chan A, Costelha S, et al. Amyloid. 2016;23(2):109‑118.
  5. Habtemariam BA, Karsten V, Attarwala H, et al. Clin Pharmacol Ther. 2021;109(2):372-382.
  6. Foster DJ, Brown CR, Shaikh S, et al. Mol Ther. 2018;26(3):708-717.
  7. Adams D, Tournev IL, Taylor MS, et al. Amyloid. 2022. Published online July 23, 2022. doi.org/10.1080/13506129.2022.2091985.
  8. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.