Hereditary Transthyretin Amyloidosis (hATTR)

Manufactured by Alnylam Pharmaceuticals, Onpattro® (patisiran) is an RNA interference (RNAi)-based drug indicated for the treatment of adults who have polyneuropathy associated with hereditary transthyretin-mediated (hATTR) amyloidosis. Onpattro contains patisiran, which is a double-stranded, transthyretin-directed, small interfering ribonucleic acid (siRNA). Onpattro decreases the synthesis of abnormal transthyretin (TTR) protein, which is misfolded and deposited as insoluble amyloid fibrils in individuals with hATTR amyloidosis. 

Onpattro is available as a lipid complex that is injected intravenously over approximately 80 minutes. The dosage for patients weighing less than 100 kg is 0.3 mg/kg once every 3 weeks, and for patients weighing 100 kg or more, it is 30 mg once every 3 weeks.1,2 

Onpattro has been granted Priority Review, Fast Track, Breakthrough Therapy, and Orphan Drug designations.3 It is approved for use only in adults.4 The drug was developed by Alnylam Pharmaceuticals, a biopharmaceutical company based in the United States. Patisiran was the first medication authorized by the US Food and Drug Administration (FDA) for the treatment of polyneuropathy associated with hATTR amyloidosis. Alnylam submitted a new drug application in December 2017, and approval was granted in August 2018.5 

Mechanism of Action

The primary site of TTR synthesis is the liver. In patients with hATTR amyloidosis, a mutation in the TTR gene results in the formation of an improperly folded and misshapen protein. The unusually shaped TTR protein accumulates in clusters called amyloid deposits or fibrils. The amyloid deposits can harm organs and nerves throughout the body. Onpattro (patisiran) is a double-stranded siRNA that attaches to the TTR gene and degrades mutant and wild-type TTR mRNA through RNA interference, thereby decreasing the amount of misfolded TTR protein in serum and TTR protein amyloid deposits in tissues.6,7 

Read more about hATTR therapies

Efficacy in Trials and Trial Results

Positive outcomes of the global phase 3 clinical trial APOLLO (NCT 01960348), a randomized, double-blind, placebo-controlled clinical research study undertaken to assess the safety and effectiveness of Onpattro, led to its approval by the FDA.5 In this trial, a total of 225 patients were randomly assigned in a 2:1 ratio to receive Onpattro or placebo for 18 months. Onpattro (0.3 mg/kg of body weight) was administered to 148 of 225 patients once every 3 weeks, while the remaining 77 patients received placebo. The primary endpoint of the study was the change from baseline in the modified Neuropathy Impairment Score +7 (mNIS+7) at 18 months. The score was used to evaluate improvements in patients’ motor function, nerve conduction, and postural blood pressure. Control of symptoms, including polyneuropathy, was measurably better in the patients who received intravenous infusions of Onpattro, as was their performance of daily activities, quality of life, and nutritional status. The Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) score, a measure of quality of life, indicated improvement in 51% of the patients treated with Onpattro vs 10% of those who received placebo.5

Warnings, Precautions, and Adverse Reactions

Adverse Reactions

The most commonly reported adverse reactions (seen in at least 5% of the Onpattro-treated patients and at least 3% more frequently than in the patients on placebo) were upper respiratory tract infections (including nasopharyngitis, upper respiratory tract infection, respiratory tract infection, pharyngitis, rhinitis, sinusitis, viral upper respiratory tract infection, and upper respiratory tract congestion) and infusion-related reactions. The latter included arthralgia or pain (back, neck, or musculoskeletal pain), flushing (facial erythema or warm skin), nausea, abdominal pain, dyspnea or cough, chest discomfort or chest pain, headache, rash, chills, dizziness, fatigue, increased heart rate or palpitations, hypotension, hypertension, and facial edema.1,5

Warnings and Precautions

During infusions, it is important to monitor the patient for symptoms and signs (eg, flushing, dyspnea, chest pain, syncope, rash, increased heart rate, facial edema) of an infusion-related reaction. Infusions may be slowed or stopped if clinically necessary. If a severe or life-threatening infusion reaction occurs, the infusion must be stopped. To lower the likelihood of an infusion-related reaction, premedication (corticosteroid, acetaminophen, and antihistamines) is required before Onpattro is administered.1 Another important precaution is to inform the patient that Onpattro can result in decreased serum levels of vitamin A. Supplementation to meet the recommended daily allowance of vitamin A is essential. In case ocular symptoms arise that suggest a vitamin A deficiency, the patient should consult an ophthalmologist.1 

Patients should also be told to inform their physician if they are pregnant or intend to become pregnant while taking Onpattro. Female patients who may become pregnant must be informed of potential risks to the developing fetus. If a patient becomes pregnant while taking Onpattro, she should be encouraged to sign the Onpattro prenatal exposure registry.1

Get full prescribing information for Onpattro at MPR


  1. ONPATTRO (patisiran) lipid complex injection, for intravenous use. Alnylam Pharmaceuticals. Revised August 2018. Accessed July 12, 2022. 
  2. Urits I, Swanson D, Swett MC, et al. A review of patisiran (ONPATTRO®) for the treatment of polyneuropathy in people with hereditary transthyretin amyloidosis [published correction appears in Neurol Ther. 2021;10(1):407]. Neurol Ther. 2020;9(2):301-315. doi:10.1007/s40120-020-00208-1
  3. Patisiran: uses, interactions, mechanism of action. DrugBank Online. Accessed July 12, 2022.
  4. ONPATTRO® (patisiran). Alnylam Pharmaceuticals. Accessed July 12, 2022.
  5. Onpattro (patisiran) for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. Clinical Trials Arena. August 17, 2018. Accessed July 12, 2022. 
  6. Onpattro (patisiran). CenterWatch. August 1, 2018. Accessed July 12, 2022.
  7. Onpattro (patisiran), Basics, side effects, reviews. GoodRx. Reviewed May 25, 2022. Accessed July 12, 2022.

Reviewed by Hasan Avcu, MD, on 7/12/2022.