Vutrisiran

Vutrisiran is a double-stranded siRNA-GalNAc conjugate 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.

• AMVUTTRA is a transthyretin-directed small interfering RNA indicated for the treatment of: the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults ( 1.1 ) the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits ( 1.2 ) 1.1 Polyneuropathy of Hereditary Transthyretin-mediated Amyloidosis AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. 1.2 Cardiomyopathy of Wild-type or Hereditary Transthyretin-mediated Amyloidosis AMVUTTRA is indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits.ICD-10: I50.9

• None. None.contraindicated

The recommended dosage of AMVUTTRA is 25 mg administered by subcutaneous injection once every 3 months. ( 2.1 ) AMVUTTRA is for subcutaneous use only and should be administered by a healthcare professional. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage of AMVUTTRA is 25 mg administered by subcutaneous injection once every 3 months [see Dosage and Administration (2.2) ] . Missed Dose If a dose is missed, administer AMVUTTRA as soon as possible. Resume dosing every 3 months from the most recently administered dose. 2.2 Administration Instructions AMVUTTRA is for subcutaneous use only and should be administered by a healthcare professional. Syringe Appearance Before and After Use Before Use After Use Image Image Preparation and Administration 1. Prepare the syringe If stored cold, allow the syringe to warm to room temperature for 30 minutes prior to use. Remove the syringe from the packaging by gripping the syringe body. Do not touch the plunger rod until ready to inject. Visually inspect the drug solution for discoloration and particulate matter prior to administration. AMVUTTRA is a sterile, preservative-free, clear, colorless-to-yellow solution. Do not use if it contains particulate matter or if it is cloudy or discolored. Check the following: Syringe is not damaged, such as cracked or leaking Needle cap is attached to the syringe Expiration date on syringe label Do not use the syringe if any issues are found while checking the syringe. 2. Choose and prepare the injection site Choose an injection site from the following areas: the abdomen, thighs, or upper arms.

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. ( 5.1 ) 5.1 Reduced Serum Vitamin A Levels and Recommended Supplementation AMVUTTRA treatment leads to a decrease in serum vitamin A levels [see Adverse Reactions (6.1) and Clinical Pharmacology (12.2) ] . Supplementation at the recommended daily allowance of vitamin A is advised for patients taking AMVUTTRA. Higher doses than the recommended daily allowance of vitamin A 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).

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Reduced Serum Vitamin A Levels and Recommended Supplementation [see Warnings and Precautions (5.1) ] The most common adverse reactions (≥5%) were pain in extremity, arthralgia, dyspnea, and vitamin A decreased. ( 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 trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of AMVUTTRA cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Two Phase 3 randomized, multi-center studies evaluated the safety of AMVUTTRA in 448 transthyretin-mediated amyloidosis (ATTR) patients, including 122 patients with hATTR-PN (HELIOS-A) and 326 patients with ATTR-CM (HELIOS-B) [see Clinical Studies (14) ] . In both studies, patients were instructed to take the recommended daily allowance of vitamin A [see Warnings and Precautions (5.1) ] . Polyneuropathy of Hereditary Transthyretin-mediated Amyloidosis In HELIOS-A, 118 patients received at least 18 months of treatment. The mean duration of treatment was 18.8 months (range: 1.7 to 19.4 months). The median patient age at baseline was 60 years and 65% of the patients were male. Seventy percent of AMVUTTRA-treated patients were Caucasian, 17% were Asian, 3% were Black, and 9% were reported as Other.

8.1 Pregnancy Risk Summary There are no available data on AMVUTTRA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. AMVUTTRA treatment leads to a decrease in serum vitamin A levels, and vitamin A supplementation is advised for patients taking AMVUTTRA. 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 AMVUTTRA and of vitamin A supplementation are unknown [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ] . In animal studies, subcutaneous administration of vutrisiran to pregnant rats resulted in developmental toxicity (reduced fetal body weight and embryofetal mortality) at doses associated with maternal toxicity (see Data ) . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Metabolism

The pharmacokinetic (PK) properties of AMVUTTRA were evaluated following a single dose in healthy subjects and multiple doses in patients with hATTR amyloidosis, as summarized in Table 2. Table 2: Pharmacokinetic Parameters of Vutrisiran Vutrisiran AUC inf = area under the concentration-time curve from the time of dosing extrapolated to infinity; AUC last = area under the concentration-time curve from the time of dosing to the last measurable concentration; C max = maximum plasma concentration; CV = coefficient of variation; RSE = relative standard error; T max = time to maximum concentration;…

• Jun 13, 2022NDANDA215515Alnylam Pharms Inc

1. 1Death41019%
2. 2Hospitalisation23811%
3. 3Intentional Dose Omission1587.4%
4. 4Fall964.5%
5. 5Product Dose Omission Issue934.4%
6. 6Fatigue844.0%
7. 7Therapy Interrupted793.7%
8. 8Dyspnoea703.3%
9. 9Gait Disturbance622.9%
10. 10Cardiac Failure602.8%
11. 11Pain In Extremity572.7%
12. 12Arthralgia542.5%
13. 13Asthenia532.5%
14. 14Atrial Fibrillation502.4%
15. 15Pain502.4%

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Vutrisiran as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy
  Recruiting · Phase 3 · Interventional · 125 enrolled · Alnylam Pharmaceuticals
  NCT07223203updated 2026-06-12
• A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
  Enrolling by invitation · Phase 3 · Interventional · 700 enrolled · Alnylam Pharmaceuticals
  NCT06679946updated 2026-02-20
• HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
  Active not recruiting · Phase 3 · Interventional · 655 enrolled · Alnylam Pharmaceuticals
  NCT04153149updated 2026-01-12
• 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

Frequently asked questions

How does Vutrisiran work?

Vutrisiran is a double-stranded siRNA-GalNAc conjugate 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 Vutrisiran used for?

According to FDA labeling, Vutrisiran carries indications including: AMVUTTRA is a transthyretin-directed small interfering RNA indicated for the treatment of: the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults ( 1.1 ) the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits ( 1.2 ) 1.1 Polyneuropathy of Hereditary Transthyretin-mediated Amyloidosis AMVUTTRA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. 1.2 Cardiomyopathy of Wild-type or Hereditary Transthyretin-mediated Amyloidosis AMVUTTRA is indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations and urgent heart failure visits.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Vutrisiran?

Vutrisiran is classified as Other nervous system drugs, Small Interfering RNA, Transthyretin-directed RNA Interaction, Gene Expression Interactions, Nucleic Acid Synthesis Inhibitors, RNA Synthetase Inhibitors, Decreased RNA Integrity, Decreased Transcription to RNA, Increased Protein Breakdown.

What are the brand names for Vutrisiran?

Vutrisiran is marketed under brand names including Amvuttra.

What are the contraindications for Vutrisiran?

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