Eplontersen

Eplontersen is an antisense oligonucleotide-GalNAc conjugate that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

• WAINUA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. WAINUA is a transthyretin-directed antisense oligonucleotide indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

• None. None.contraindicated

• The recommended dosage of WAINUA is 45 mg administered by subcutaneous injection once monthly. ( 2.1 ) • Administer WAINUA into the abdomen or upper thigh region; the back of the upper arm can be used if a healthcare provider or caregiver administers the injection. ( 2.2 ) • The prefilled syringe must be administered by a healthcare provider. ( 2.4 ) 2.1 Recommended Dosage The recommended dosage of WAINUA is 45 mg administered by subcutaneous injection once monthly [see Dosage and Administration (2.2) ] . Missed Dose Administer WAINUA as soon as possible after a missed dose. Resume dosing at monthly intervals from the date of the most recently administered dose. 2.2 General Administration Instructions Each autoinjector and prefilled syringe contains a single dose of WAINUA. Prior to administration of the autoinjector or prefilled syringe: • Do not use if WAINUA has been dropped or damaged, appears to be tampered with, or if the expiration date has passed. • Remove WAINUA from the refrigerator 30 minutes prior to the injection to reach room temperature. Do not use other warming methods. • Visually inspect WAINUA before use. The solution should appear colorless to yellow. Do not use if cloudiness, particulate matter, or discoloration is observed. To deliver a 45 mg dose of WAINUA, administer the entire contents of one autoinjector or prefilled syringe [see Dosage and Administration (2.3) , (2.4) ] , as a subcutaneous injection in the upper thigh or the abdomen.

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 WAINUA treatment leads to a decrease in serum vitamin A levels [see Adverse Reactions (6.1) , Use in Specific Populations (8.1) , and Clinical Pharmacology (12.2) ] . Supplementation at the recommended daily allowance of vitamin A is advised for patients taking WAINUA. 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 WAINUA, 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, dry eyes).

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) ]. Most common adverse reactions (that occurred in at least 9% of patients treated with WAINUA) were vitamin A decreased and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 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 WAINUA cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In Study 1 [see Clinical Studies (14) ] , a total of 144 patients with polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) were randomized to WAINUA and received at least one dose of WAINUA. Of these, 141 patients received at least 6 months of treatment and 107 patients received at least 12 months of treatment. The mean duration of treatment was 15 months (range: 1.9 to 19.4 months). The median patient age at baseline was 52 years and 69% of the patients were male. Seventy-eight percent of patients treated with WAINUA were White, 15% were Asian, 4% were Black, 2% were reported as other races, and <1% were multiple races. Fifty-nine percent of patients had the Val30Met variant in the transthyretin gene; the remaining patients had one of 19 other variants.

8.1 Pregnancy Risk Summary There are no available data on WAINUA use in pregnant women to inform drug-associated risk of adverse developmental outcomes. WAINUA treatment leads to a decrease in serum vitamin A levels, and vitamin A supplementation is advised for patients taking WAINUA. Vitamin A is essential for normal embryofetal development; however, excessive levels of vitamin A are associated with adverse developmental effects. The effect of vitamin A supplementation on the fetus in the setting of a reduction in maternal serum TTR caused by WAINUA administration is unknown [see Clinical Pharmacology (12.2) and Warnings and Precautions (5.1) ] . No adverse developmental effects were observed when eplontersen or a mouse-specific surrogate was administered to mice prior to mating and continuing throughout organogenesis [see Animal Data ] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Metabolism

The pharmacokinetic (PK) properties of WAINUA were evaluated following subcutaneous administration of single and multiple doses (once every 4 weeks) in healthy subjects and multiple doses (once every 4 weeks) in patients with hATTR amyloidosis. Eplontersen C max and AUC showed a slightly greater than dose-proportional increase following single subcutaneous doses ranging from 45 to 120 mg (i.e., 1- to 2.7-times the recommended dose) in healthy volunteers.

• Dec 21, 2023NDANDA217388Astrazeneca Ab

1. 1Death148.8%
2. 2Fatigue138.1%
3. 3Nausea127.5%
4. 4Neuropathy Peripheral127.5%
5. 5Pain95.6%
6. 6Vomiting74.4%
7. 7Diarrhoea63.8%
8. 8Hypoaesthesia63.8%
9. 9Pain In Extremity63.8%
10. 10Paraesthesia63.8%
11. 11Product Dose Omission Issue63.8%
12. 12Vision Blurred63.8%
13. 13Constipation53.1%
14. 14Drug Ineffective53.1%
15. 15Pruritus53.1%

The 10 most recently updated of 14 ClinicalTrials.gov registrations naming Eplontersen as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM
  Not yet recruiting · Phase 2 · Interventional · 326 enrolled · AstraZeneca
  NCT07608354updated 2026-06-10
• EPIC-ATTR: A Study to Evaluate the Effect of Eplontersen on the Transthyretin Reduction and Long-term Safety in Chinese Subjects With Transthyretin Amyloid Cardiomyopathy
  Active not recruiting · Phase 3 · Interventional · 64 enrolled · AstraZeneca
  NCT06194825updated 2026-06-09
• Non-interventional Study of Patients With Transthyretin (ATTR) Amyloidosis
  Recruiting · Observational · 1,850 enrolled · AstraZeneca
  NCT06465810updated 2026-05-26
• The Eplontersen Pregnancy and Lactation Outcomes Study
  Recruiting · Observational · 10 enrolled · AstraZeneca
  NCT07205666updated 2026-05-01
• An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
  Enrolling by invitation · Phase 3 · Interventional · 1,400 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05667493updated 2026-04-17
• A Study to Assess the Long-Term Safety and Efficacy of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Patients With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
  Active not recruiting · Phase 3 · Interventional · 151 enrolled · Ionis Pharmaceuticals, Inc.
  NCT05071300updated 2025-12-04
• CARDIO-TTRansform Magnetic Resonance Imaging (MRI) Sub-study
  Active not recruiting · Observational · 150 enrolled · Ionis Pharmaceuticals, Inc.
  NCT06073574updated 2025-11-28
• The CARDIO-TTRansform Scintigraphy Sub-study
  Active not recruiting · Observational · 150 enrolled · Ionis Pharmaceuticals, Inc.
  NCT06073587updated 2025-11-28
• CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM)
  Active not recruiting · Phase 3 · Interventional · 1,438 enrolled · Ionis Pharmaceuticals, Inc.
  NCT04136171updated 2025-08-08
• carDIo-ttranSSfOrm nucLEar Imaging Study
  Terminated · Observational · 4 enrolled · Oregon Health and Science University
  NCT05259072updated 2025-01-29

Frequently asked questions

How does Eplontersen work?

Eplontersen is an antisense oligonucleotide-GalNAc conjugate that causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

What is Eplontersen used for?

According to FDA labeling, Eplontersen carries indications including: WAINUA is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. WAINUA is a transthyretin-directed antisense oligonucleotide 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 Eplontersen?

Eplontersen is classified as Other nervous system drugs, Antisense Oligonucleotide, Transthyretin-directed RNA Interaction, Gene Expression Interactions, Decreased RNA Integrity, Increased Protein Breakdown.

What are the brand names for Eplontersen?

Eplontersen is marketed under brand names including Wainua.

What are the contraindications for Eplontersen?

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