ONPATTRO® (patisiran)—the first FDA-approved RNAi therapeutic1


ONPATTRO is indicated for the treatment of the polyneuropathy of hATTR amyloidosis in adults. A double-stranded small interfering ribonucleic acid (siRNA), ONPATTRO is formulated for targeted delivery to hepatocytes, the primary source of TTR protein production.1-3

Mechanism of action for ONPATTRO® (patisiran)

in tissues

Fewer amyloid
in tissues

ONPATTRO harnesses the endogenous RNAi pathway, which causes the degradation of variant and wild-type TTR mRNA and reduces production of TTR protein1

Reducing the serum TTR protein leads to a decrease in the amount of amyloid deposits that accumulate in tissues1,4,5

Transthyretin (TTR) protein in a patient with hATTR amyloidosis2,3

Mechanism of action for ONPATTRO® (patisiran) Mechanism of action for ONPATTRO® (patisiran)


Primary site of TTR production

Variants lead to misfolding of TTR protein

Misfolded TTR protein forms amyloid deposits in tissues

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

Watch the video to see
how ONPATTRO works

ONPATTRO® (patisiran) Mechanism of Action video

Reducing the pathogenic TTR protein leads to a
reduction in amyloid deposits in tissues.1,4,5

In the APOLLO study, treatment with ONPATTRO® (patisiran) led to a…

Rapid and powerful reduction in serum TTR1

84% mean reduction of serum TTR at 18 months1,6,a

Mean serum transthyretin (TTR) reduction with ONPATTRO® (patisiran)

aBars represent SEM (standard error of the mean).


Adapted from New England Journal of Medicine, Adams D, Gonzalez-Duarte A, O’Riordan WD, et al, “Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis,” 379(1). Copyright © 2018 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.


Approximately 80% reduction in mean serum TTR within 10 to 14 days after a single dose1

88% mean maximum serum TTR reduction from baseline over 18 months1

TTR reduction was maintained for >4 years with continued dosing in an ongoing global open-label extension (OLE) study7

  • Reduction observed regardless of TTR variant, sex, age, or race1
  • Serum TTR was evaluated in patients with hATTR amyloidosis with polyneuropathy treated with 0.3 mg/kg ONPATTRO via intravenous infusion once every 3 weeks1

Important Safety Information and Indication

Important Safety Information

Infusion-Related Reactions

Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO® (patisiran). In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation

ONPATTRO 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 ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum 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 ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%).


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

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


1. ONPATTRO Prescribing Information. Cambridge, MA: Alnylam Pharmaceuticals, Inc.

2. Holmgren G, Steen L, Ekstedt J, et al. Clin Genet. 1991;40(3):242-246.

3. Soprano DR, Herbert J, Soprano KJ, Schon EA, Goodman DS. J Biol Chem. 1985;260(21):11793-11798.

4. Adams D, Coelho T, Conceicao I, et al. Slides presented at: American Academy of Neurology; April 26, 2017; Boston, MA.

5. Tsuchiya A, Yazaki M, Kametani F, et al. Liver Transpl. 2008;14(4):563-570.

6. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.

7. González-Duarte A, Coelho T, Adams D, et al. Poster presented at: AANEM Annual Meeting; October 10-13, 2018; Washington, DC.