How AMVUTTRA works

AMVUTTRA® (vutrisiran) Mechanism of Action Hero Image.
AMVUTTRA® (vutrisiran) Mechanism of Action Hero Image.
How AMVUTTRA works
AMVUTTRA® mechanism of action
Watch this video to learn how AMVUTTRA works

See how treatment with AMVUTTRA led to a rapid knockdown of TTR protein in serum.1

MOA

AMVUTTRA® (vutrisiran) Mechanism of Action Hero Image
AMVUTTRA® (vutrisiran) Mechanism of Action Hero Image

Rapid knockdown of TTR is powered by RNAi1,2

What is AMVUTTRA?

AMVUTTRA is an RNAi therapeutic indicated for the treatment of the polyneuropathy of hATTR amyloidosis in adults.2 AMVUTTRA deploys the body's natural silencing complex, reducing the production of the disease-causing protein.2

RNAi=RNA interference.

Choose below to see:

Effect of TTR protein misfolding
Mechanism of action for AMVUTTRA

Without intervention, patients face irreversible damage3-6

Image of TTR proteins dissociating, misfolding, and forming amyloid deposits in the tissues of a patient with hATTR amyloidosis.
Liver:
Primary site of TTR production
Image of TTR proteins dissociating, misfolding, and forming amyloid deposits in the tissues of a patient with hATTR amyloidosis.
Variants lead to misfolding of TTR proteins
Progressive symptoms
Image of TTR proteins dissociating, misfolding, and forming amyloid deposits in the tissues of a patient with hATTR amyloidosis.
Misfolded TTR protein
forms amyloid deposits
in tissues

Reduction of amyloid deposits2,7,8

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 mRNA2
Image of AMVUTTRA™ (vutrisiran) being delivered to hepatocytes, the primary source of TTR protein production.
This results in the rapid knockdown of TTR protein in serum2,7,8
Fewer amyloid deposits in tissues2,7
Image of AMVUTTRA™ (vutrisiran) being delivered to hepatocytes, the primary source of TTR protein production.
This results in the rapid knockdown of TTR protein in serum2,7,8

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

In the HELIOS-A study…

Treatment with AMVUTTRA led to rapid knockdown of TTR as early as 3 weeks1,a

AMVUTTRA achieved sustained knockdown of TTR over 18 months, with a mean TTR knockdown level as high as 88%1,b,c

Percent change from baseline in serum TTR levels1,9

Graph showing mean reduction in serum TTR.

aFirst measured at 3 weeks. bBars represent SEM. cTTR knockdown level is demonstrated through serum TTR reduction.

KD=knockdown; SEM=standard error of the mean.

Percent change from baseline in serum TTR levels1,9
Graph showing mean reduction in serum TTR.

aFirst measured at 3 weeks. bBars represent SEM. cTTR knockdown level is demonstrated through serum TTR reduction.

KD=knockdown; SEM=standard error of the mean.

  • Serum TTR was evaluated in patients with hATTR amyloidosis with polyneuropathy treated with 25 mg AMVUTTRA via subcutaneous injection once every 3 months2
  • AMVUTTRA rapidly knocked down TTR as early as 3 weeks, with a mean TTR knockdown as high as 88% over 18 months1
  • With AMVUTTRA, similar rapid knockdown in serum TTR was observed regardless of V30M variant status, previous TTR stabilizer use, sex, age, weight, or race2,10

AMVUTTRA achieves sustained knockdown of TTR with a subcutaneous injection 4 times per year.1,2

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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. Adams D, Tournev IL, Taylor MS, et al. Amyloid. 2023;30(1):18-26.
  2. AMVUTTRA Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.
  3. Holmgren G, Steen L, Ekstedt J, et al. Clin Genetics. 1991;40(3):242-246.
  4. Soprano DR, Herbert J, Soprano KJ, et al. J Biol Chem. 1985;260(21):11793-11798.
  5. Conceição I, González-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21(1):5-9.
  6. Ando Y, Nakamura M, Araki S. Arch Neurol. 2013;62(7):1057-1062.
  7. Butler JS, Chan A, Costelha S, et al. Amyloid. 2016;23(2):109‑118.
  8. Habtemariam BA, Karsten V, Attarwala H, et al. Clin Pharmacol Ther. 2021;109(2):372-382.
  9. Adams D, González-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.
  10. Data on file. Alnylam Pharmaceuticals, Inc.