How AMVUTTRA works

What is AMVUTTRA™?

AMVUTTRA is an RNAi therapeutic indicated for the treatment of the polyneuropathy of hATTR amyloidosis in adults1

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

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

mRNA=messenger RNA; RNA=ribonucleic acid; RNAi=RNA interference.

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

In the HELIOS-A study…

Treatment with AMVUTTRA led to rapid, powerful, and sustained reduction in serum TTR7,8

88% mean reduction of serum TTR with dosing once every 3 months1,8,9,a
HELIOS-A study graph

aBars represent SEM (standard error of the mean).

88% mean reduction of serum TTR with dosing once every 3 months1,8,9,a
HELIOS-A study graph

aBars represent 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 months1
  • Similar reduction in serum TTR was observed regardless of V30M variant status, prior TTR stabilizer use, sex, age, weight, or race1,10

AMVUTTRA is formulated to enable dosing via subcutaneous injection 4 times per year.1

AMVUTTRA mechanism of action
Preview image of the AMVUTTRA™ (vutrisiran) mechanism of action video
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Watch this video to learn how AMVUTTRA works

See how treatment with AMVUTTRA may reduce serum TTR protein and TTR protein deposits in tissues.

Up next Learn more about the HELIOS-A study design

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 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 Genet. 1991;40:242-246.
  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. 2020.
  6. Foster DJ, Brown CR, Shaikh S, et al. Mol Ther. 2018;26(3):708-717.
  7. Adams D, Tournev I, Taylor M, et al. Slides presented at American Academy of Neurology; April 17-22, 2021.
  8. Adams D, Tournev I, Taylor M, et al. Slides presented at la Société Francophone du Nerf Périphérique (SFNP); January 21-22, 2022.
  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.

Important Safety Information and Indication

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 arthralgia (11%), dyspnea (7%), and vitamin A decreased (7%).

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

For patients

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 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.