Patisiran

Patisiran is a double-stranded siRNA that causes degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

• ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. ONPATTRO contains a transthyretin-directed small interfering RNA and is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

• None.contraindicated

For patients weighing less than 100 kg, the recommended dosage is 0.3 mg/kg every 3 weeks by intravenous infusion. For patients weighing 100 kg or more, the recommended dosage is 30 mg ( 2.1 ) Premedicate with a corticosteroid, acetaminophen, and antihistamines ( 2.2 ) Filter and dilute prior to administration ( 2.3 ) Infuse over approximately 80 minutes ( 2.4 ) 2.1 Dosing Information ONPATTRO should be administered by a healthcare professional. ONPATTRO is administered via intravenous (IV) infusion. Dosing is based on actual body weight. For patients weighing less than 100 kg, the recommended dosage is 0.3 mg/kg once every 3 weeks. For patients weighing 100 kg or more, the recommended dosage is 30 mg once every 3 weeks. Missed Dose If a dose is missed, administer ONPATTRO as soon as possible. If ONPATTRO is administered within 3 days of the missed dose, continue dosing according to the patient's original schedule. If ONPATTRO is administered more than 3 days after the missed dose, continue dosing every 3 weeks thereafter. 2.2 Required Premedication All patients should receive premedication prior to ONPATTRO administration to reduce the risk of infusion-related reactions (IRRs) [see Warnings and Precautions (5.1) ] .

Infusion-related reactions: Monitor for signs and symptoms during infusion. Slow or interrupt the infusion if clinically indicated. Discontinue the infusion if a serious or life-threatening infusion-related reaction occurs ( 5.1 ) Reduced serum vitamin A levels and recommended supplementation: Supplement with the recommended daily allowance of vitamin A. Refer to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur ( 5.2 ) 5.1 Infusion-Related Reactions Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In clinical studies, all patients received premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) to reduce the risk of IRRs. In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated patients. Among ONPATTRO-treated patients who experienced an IRR, 79% experienced the first IRR within the first 2 infusions. The frequency of IRRs decreased over time. IRRs led to infusion interruption in 5% of patients. IRRs resulted in permanent discontinuation of ONPATTRO in less than 1% of patients in clinical studies. Across clinical studies, the most common symptoms (reported in greater than 2% of patients) of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache [see Adverse Reactions (6.1) ] . Severe hypotension and syncope have been reported as symptoms of IRRs in the expanded access program and postmarketing setting.

The following clinically significant adverse reactions are described elsewhere in the labeling: Infusion-Related Reactions [see Warnings and Precautions (5.1) ] The most frequently reported adverse reactions (that occurred in at least 10% of ONPATTRO-treated patients and at least 3% more frequently than on placebo) were upper respiratory tract infections and infusion-related reactions ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alnylam Pharmaceuticals at 1-877-256-9526 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of ONPATTRO cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. A total of 224 patients with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) received ONPATTRO in the placebo-controlled and open-label clinical studies, including 186 patients exposed for at least 1 year, 137 patients exposed for at least 2 years, and 52 patients exposed for at least 3 years. In the placebo-controlled study, 148 patients received ONPATTRO for up to 18 months (mean exposure 17.7 months). Baseline demographic and disease characteristics were generally similar between treatment groups. The median age of study patients was 62 years and 74% were male. Seventy-two percent of study patients were Caucasian, 23% were Asian, 2% were Black, and 2% were reported as other.

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ONPATTRO during pregnancy. Physicians are encouraged to enroll pregnant patients, or pregnant women may register themselves in the program by calling 1-877-256-9526 or by contacting alnylampregnancyprogram@iqvia.com. Risk Summary There are no available data on ONPATTRO use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. ONPATTRO treatment leads to a decrease in serum vitamin A levels, and vitamin A supplementation is advised for patients taking ONPATTRO. Vitamin A is essential for normal embryofetal development; however, excessive levels of vitamin A are associated with adverse developmental effects. The effects on the fetus of a reduction in maternal serum TTR caused by ONPATTRO and of vitamin A supplementation are unknown [see Clinical Pharmacology (12.2) , Warnings and Precautions (5.2) ] . In animal studies, intravenous administration of patisiran lipid complex (patisiran-LC) to pregnant rabbits resulted in developmental toxicity (embryofetal mortality and reduced fetal body weight) at doses that were also associated with maternal toxicity.

Metabolism

Following a single intravenous administration, systemic exposure to patisiran increases in a linear and dose-proportional manner over the range of 0.01 to 0.5 mg/kg. Greater than 95% of patisiran in the circulation is associated with the lipid complex.

• Aug 10, 2018NDANDA210922Alnylam Pharms Inc

1. 1Death2689.6%
2. 2Product Dose Omission Issue1766.3%
3. 3Fatigue1736.2%
4. 4Hospitalisation1324.7%
5. 5Infusion Related Reaction1284.6%
6. 6Fall1154.1%
7. 7Asthenia1144.1%
8. 8Intentional Dose Omission1114.0%
9. 9Cardiac Failure973.5%
10. 10Dyspnoea913.3%
11. 11Malaise893.2%
12. 12Inappropriate Schedule Of Product Administration843.0%
13. 13Nausea833.0%
14. 14Diarrhoea802.9%
15. 15Dizziness792.8%

The 10 most recently updated of 17 ClinicalTrials.gov registrations naming Patisiran as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Patisiran-Lipid Nanoparticle (LNP) Pregnancy Surveillance Program
  Recruiting · Observational · 10 enrolled · Alnylam Pharmaceuticals
  NCT05040373updated 2026-06-01
• Spectrum of Peripheral and Autonomic Neuropathies in Patients With aTTRwt Amyloidosis and Response to Patisiran Therapy
  Completed · Early phase 1 · Interventional · 10 enrolled · Austin Neuromuscular Center
  NCT05023889updated 2026-05-22
• APOLLO-B: A Study to Evaluate Patisiran in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
  Completed · Phase 3 · Interventional · 360 enrolled · Alnylam Pharmaceuticals
  NCT03997383updated 2026-04-20
• Monitoring of Early Disease Progression in Hereditary Transthyretin Amyloidosis
  Completed · Observational · 37 enrolled · The Cleveland Clinic
  NCT03431896updated 2026-03-12
• HELIOS-A: A Study of Vutrisiran (ALN-TTRSC02) in Patients With Hereditary Transthyretin Amyloidosis (hATTR Amyloidosis)
  Completed · Phase 3 · Interventional · 164 enrolled · Alnylam Pharmaceuticals
  NCT03759379updated 2026-01-12
• Myocardial Effects in Patients With ATTRv With Polyneuropathy Treated With Patisiran or Vutrisiran
  Active not recruiting · Observational · 20 enrolled · Rennes University Hospital
  NCT05873868updated 2026-01-05
• Evuzamitide in PET/CT to Measure Potential Therapeutic Response in ATTR
  Completed · Phase 2 · Interventional · 10 enrolled · Columbia University
  NCT05635045updated 2025-07-18
• Expanded Access Protocol of Patisiran for Patients With Hereditary ATTR Amyloidosis (hATTR)
  Approved for marketing · Expanded access · Alnylam Pharmaceuticals
  NCT02939820updated 2024-05-20
• Patisiran in Patients With Hereditary Transthyretin-mediated Amyloidosis (hATTR Amyloidosis) Disease Progression Post-Liver Transplant
  Completed · Phase 3 · Interventional · 24 enrolled · Alnylam Pharmaceuticals
  NCT03862807updated 2024-04-22
• APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis
  Completed · Phase 3 · Interventional · 225 enrolled · Alnylam Pharmaceuticals
  NCT01960348updated 2024-04-22

Frequently asked questions

How does Patisiran work?

Patisiran is a double-stranded siRNA that causes degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

What is Patisiran used for?

According to FDA labeling, Patisiran carries indications including: ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. ONPATTRO contains a transthyretin-directed small interfering RNA and is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Patisiran?

Patisiran is classified as Other nervous system drugs, Small Interfering RNA, Transthyretin-directed RNA Interaction, Decreased Protein Synthesis, Decreased RNA Integrity, Increased Protein Breakdown.

What are the brand names for Patisiran?

Patisiran is marketed under brand names including Onpattro.

What are the contraindications for Patisiran?

Patisiran labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.