WAINUA - AstraZeneca Pharmaceuticals LP

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

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

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Injection: 45 mg/0.8 mL of eplontersen as a clear, colorless-to-yellow solution available in a single dose autoinjector or a single-dose prefilled syringe.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

None.

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

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) ].

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

11 DESCRIPTION

DESCRIPTION SECTION

Eplontersen is a transthyretin-directed antisense oligonucleotide (ASO), covalently linked to a ligand containing three N-acetyl galactosamine (GalNAc) residues to enable delivery of the ASO to hepatocytes. WAINUA contains eplontersen sodium as the active ingredient. Eplontersen sodium is a white to yellow solid and it is freely soluble in water and in phosphate buffer. The molecular formula of eplontersen sodium is C 296 H 417 N 77 O 156 P 20 S 13 Na 20 and the molecular weight is 9046.1 daltons. The chemical name of eplontersen sodium is DNA, d([2′-O-(2-methoxyethyl)]m5rU-sp-[2′-O-(2-methoxyethyl)]m5rC-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]rG-G-sp-T-sp-T-sp-A-sp-m5C-sp-A-sp-T-sp-G-sp-A-sp-A-sp-[2′-O-(2-methoxyethyl)]rA-[2′-O-(2-methoxyethyl)]m5rU-[2′-O-(2-methoxyethyl)]m5rC-sp-[2′-O-(2-methoxyethyl)]m5rC-sp-[2′-O-(2-methoxyethyl)]m5rC), 5′-[26-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]-14,14-bis[[3-[[6-[[2-(acetylamino)-2-deoxy-β-D-galactopyranosyl]oxy]hexyl]amino]-3-oxopropoxy]methyl]-8,12,19-trioxo-16-oxa-7,13,20-triazahexacos-1-yl hydrogen phosphate], sodium salt (1:20). The structure of eplontersen sodium is presented below: WAINUA is a sterile, preservative-free, aqueous solution for subcutaneous injection supplied in a single dose autoinjector or single-dose prefilled syringe. Each dose contains 45 mg eplontersen (equivalent to 47 mg eplontersen sodium) in 0.8 mL of solution. The solution also contains 0.868 mg dibasic sodium phosphate, anhydrous (buffering agent); 0.238 mg monobasic sodium phosphate, dihydrate (buffering agent); 4.2 mg sodium chloride (tonicity modifier); water for injection; and may include hydrochloric acid and/or sodium hydroxide for pH adjustment between 6.9 - 7.9. Each dose of WAINUA injection contains less than 5 mg of sodium and less than 5 mg of phosphorus.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

The efficacy of WAINUA was demonstrated in a randomized, open-label, multicenter clinical trial in adult patients with polyneuropathy caused by hATTR amyloidosis (Study 1; NCT04136184). Patients were randomized in a 6:1 ratio to receive either 45 mg of WAINUA once every 4 weeks (N=144), or 284 mg of inotersen once per week (N=24), respectively, as subcutaneous injections. Ninety-seven percent of WAINUA-treated patients and 83% of inotersen-treated patients completed at least 35 weeks of the assigned treatment. Efficacy assessments were based on a comparison of the WAINUA arm of Study 1 with an external placebo group (N=60) in another study (NCT01737398) composed of a comparable population of adult patients with polyneuropathy caused by hATTR amyloidosis. The efficacy endpoints were the change from baseline to Week 35 in the modified Neuropathy Impairment Scale+7 (mNIS+7) composite score and the change from baseline to Week 35 in the Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) total score. The mNIS+7 is an objective assessment of neuropathy and comprises the neuropathy impairment score (NIS) and Modified +7 composite scores. In the version of the mNIS+7 used in the trial, the NIS objectively measures deficits in cranial nerve function, muscle strength, reflexes, and sensations, and the Modified +7 assesses heart rate response to deep breathing, quantitative sensory testing (touch-pressure and heat-pain), and peripheral nerve electrophysiology. The validated version of the mNIS+7 score used in the trial has a range of -22.3 to 346.3 points, with higher scores representing a greater severity of disease. The clinical meaningfulness of effects on the mNIS+7 was assessed by the change from baseline to Week 35 in Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) total score. The Norfolk QoL-DN scale is a patient-reported assessment that evaluates the subjective experience of neuropathy in the following domains: physical functioning/large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy. The version of the Norfolk QoL-DN that was used in the trial has a range from -4 to 136 points, with higher scores representing greater impairment. Treatment with WAINUA resulted in statistically significant improvements in the mNIS+7 and the Norfolk QoL-DN total scores, compared to the external placebo control (p

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Recommended Vitamin A Supplementation Inform patients that WAINUA treatment leads to a decrease in vitamin A levels measured in the serum. Instruct patients to take the recommended daily allowance of vitamin A. Advise patients to contact their healthcare provider if they experience ocular symptoms suggestive of vitamin A deficiency (e.g., night blindness, dry eyes) and refer them to an ophthalmologist if they develop these symptoms [see Warnings and Precautions (5.1) ] . Pregnancy Instruct patients that if they are pregnant or plan to become pregnant while taking WAINUA they should inform their healthcare provider. Advise patients of the potential risk to the fetus, including that WAINUA treatment leads to a decrease in serum vitamin A levels [see Use in Special Populations (8.1) ] . Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 ©AstraZeneca 2026

PATIENT INFORMATION

SPL UNCLASSIFIED SECTION

PATIENT INFORMATION WAINUA [way-noo’-ah] (eplontersen) injection, for subcutaneous use What is WAINUA? WAINUA is a prescription medicine used to treat adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis. It is not known if WAINUA is safe and effective in children. Before you take WAINUA, tell your healthcare provider if you: • are pregnant or plan to become pregnant. It is not known if WAINUA can harm your unborn baby. Changes in vitamin A levels and vitamin A supplementation related to use of WAINUA may harm your unborn baby. Tell your healthcare provider if you become pregnant or think you may be pregnant while taking WAINUA. • are breastfeeding or plan to breastfeed. It is not known if WAINUA can pass into your breast milk or harm your baby. Talk with your healthcare provider about the best way to feed your baby while you are using WAINUA. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take: • Vitamin A or beta-carotene supplements. Ask your healthcare provider or pharmacist if you are not sure if you take any of these medicines. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. How should I take WAINUA? WAINUA comes in a single dose autoinjector and in a single dose prefilled syringe. If you are prescribed the single dose autoinjector: • Read the detailed Instructions for Use that come with your WAINUA single dose autoinjector. • Your healthcare provider will show you or your caregiver how to inject WAINUA using the single dose autoinjector the first time. • If you or your caregiver have any questions, ask your healthcare provider. • WAINUA is injected under your skin (subcutaneously) in your stomach area (abdomen), or the front of your upper legs (thighs) by you or a caregiver. A caregiver may also give you an injection of WAINUA in the outer area of your upper arm. • Follow your healthcare provider’s instructions on when to inject WAINUA. • WAINUA should be injected 1 time on the same day of each month. • If you miss a dose, take the missed dose as soon as possible. Then inject WAINUA 1 month from the date of your last dose to get back on a monthly dosing schedule. If you have questions about your schedule, ask your healthcare provider. If you are prescribed the single-dose prefilled syringe: • Only a healthcare provider may inject WAINUA using the single dose prefilled syringe. What are the possible side effects of WAINUA? WAINUA may cause side effects, including: • Low vitamin A level. Low vitamin A level is a serious, but common side effect of treatment with WAINUA. Your healthcare provider should tell you to take vitamin A supplements while using WAINUA. Do not take more than the amount of vitamin A your healthcare provider has recommended. Call your healthcare provider if you develop eye problems such as difficulty seeing at night or in low lit areas (night blindness), or dry eyes. If you develop eye problems while receiving treatment with WAINUA, your healthcare provider should send you to see an eye doctor (ophthalmologist). The most common side effects of WAINUA include decreased vitamin A and vomiting. These are not all of the possible side effects of WAINUA. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800-FDA-1088. How should I store WAINUA? • Store WAINUA in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton. • WAINUA can also be kept at room temperature that is no higher than 86°F (30°C) in the original carton for up to 6 weeks. • Do not let WAINUA reach temperatures above 86°F (30°C). • If you do not use WAINUA kept at room temperature within 6 weeks, throw it away. • Do not freeze. • Do not expose WAINUA to heat. • Protect from light. Keep WAINUA and all medicines out of the reach of children. General information about the safe and effective use of WAINUA. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use WAINUA for a condition for which it was not prescribed. Do not give WAINUA to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about WAINUA that is written for health professionals. What are the ingredients in WAINUA? Active ingredient: eplontersen sodium. Inactive ingredients: dibasic sodium phosphate, anhydrous; monobasic sodium phosphate, dihydrate; sodium chloride; water for injection, and may include hydrochloric acid and sodium hydroxide for pH adjustment. Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 ©AstraZeneca 2026 For more information, go to https://www.wainua.com or call 1-800-236-9933. If you still have questions, contact your healthcare provider. This Patient Information has been approved by the U.S. Food and Drug Administration Approved: 04/2026

INSTRUCTIONS FOR USE

INSTRUCTIONS FOR USE SECTION

INSTRUCTIONS FOR USE WAINUA [way-noo’-ah] (eplontersen) injection, for subcutaneous use Single-dose autoinjector 45 mg/0.8 mL This Instructions for Use contains information on how to inject WAINUA using the autoinjector. Read this Instructions for Use before you start using the WAINUA autoinjector and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition and your treatment. Your healthcare provider should show you or your caregiver how to use the autoinjector the right way. If you or your caregiver have any questions, talk to your healthcare provider. Important information you need to know before using WAINUA Keep your autoinjector and all medicines out of the sight and reach of children. • WAINUA is for use by injection under the skin (subcutaneous use) only. • Each WAINUA autoinjector contains 1 dose and can only be used 1 time. • Do not share your autoinjector with anyone. • Do not use the autoinjector if it has: ∘ been frozen ∘ been dropped, damaged, or appears to be tampered with ∘ passed the expiration date (EXP) Storing the WAINUA autoinjector • Store the WAINUA autoinjector in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton to protect from light. Do not freeze. • If needed, the WAINUA autoinjector may be stored at room temperature up to 86°F (30°C) for up to a maximum of 6 weeks protected from light. • If you do not use the WAINUA autoinjector within 6 weeks at room temperature, throw it away in an FDA-cleared sharps disposal container. • Keep the autoinjector in the carton until ready to use. Keep your autoinjector and all medicines out of the sight and reach of children. Overview of your WAINUA autoinjector Do not remove the cap until just before you give the injection. Do not touch the orange needle guard. How does the WAINUA autoinjector work? Make sure you read the entire instructions before uncapping and injecting. The injection starts automatically when the orange needle guard is pushed against the skin. The autoinjector must be held firmly against the skin to allow it to deliver the full dose of the medicine. The injection is complete only when the orange plunger rod fills the viewing window (See “Overview of your WAINUA autoinjector”, After use). Preparing to inject WAINUA using the autoinjector Step 1 – Gather supplies for your injection Step 2 – Wait 30 minutes Keep the autoinjector in the original carton after removing it from the refrigerator and allow to come to room temperature for 30 minutes before injecting. • Do not warm up in any other way. For example, do not warm it in a microwave or hot water, or near other heat sources. • Keep it away from light or direct sunlight. Step 3 – Remove from the carton and check the autoinjector and medicine Check the autoinjector for damage. • Do not use if damaged. Check the expiration (EXP) date. • Do not use if the expiration date has passed. Check the liquid through the viewing window. • It is normal to see small air bubbles in the liquid. • The liquid should be clear and colorless to slightly yellow. • Do not use if the liquid is cloudy, discolored, or contains large particles. Injecting with your autoinjector Step 4 – Choose an injection site You or your caregiver can inject in the front of your thigh or your stomach (abdomen). A caregiver may inject you in the back of your upper arm. Do not try to inject yourself in the back of your upper arm. For each injection, choose an injection site that is at least 1 inch (3 cm) away from where you last injected. Do not inject: • into the 2-inch (5-cm) area around your belly button • where the skin is red, warm, tender, bruised, scaly, or hard • into scars, damaged, discolored, or tattooed skin • through clothing Step 5 – Wash your hands and clean the injection site Wash your hands well with soap and water. Clean the injection site with an alcohol wipe or with soap and water. Let the site air dry. • Do not touch the cleaned area before injecting. Step 6 – Pull off the cap Hold the autoinjector body with 1 hand, and carefully pull the cap straight off with your other hand. Do not twist it off. The orange needle guard is now exposed and the needle is hidden underneath. • Throw away (dispose of) the cap. • Do not touch the needle or push on the orange needle guard with your finger. • Do not recap the autoinjector. This could cause the medicine to come out too soon or damage the autoinjector. Step 7 – Inject WAINUA using the autoinjector Inject the medicine using the autoinjector by following the steps in figures a, b, c and d . When injecting, press and hold the autoinjector for 10 seconds until the orange plunger fills the viewing window. You may hear a first ‘click’ at the start of the injection and a second ‘click’ at the end of injection. This is normal. Do not move or change the position of the autoinjector after the injection has started. Position the autoinjector. • Place the orange needle guard flat against your skin (90-degree angle). • Make sure you can see the viewing window. Step 8 – Check the viewing window Check the viewing window to make sure all the medicine has been injected. If the orange plunger rod does not fill the viewing window, you may not have received the full dose. If this happens or if you have other concerns, contact your healthcare provider. Step 9 – Check the injection site There may be a small amount of blood or liquid where you injected. This is normal. If needed, press a cotton ball or gauze on the area and apply a small bandage. Step 10 – Throw away (dispose of) the used autoinjector Put the used autoinjector in an FDA-cleared sharps disposal container right away after use. Do not throw away the autoinjector in your household trash. Disposal guidelines If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: • made of a heavy-duty plastic, • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, • upright and stable during use, • leak-resistant, and • properly labeled to warn of hazardous waste inside the container. When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and autoinjectors. For more information about safe sharps disposal, and for specific information about sharps disposal in the area that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal . Do not throw away (dispose of) your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container. For more information, go to https://www.wainua.com or call 1-800-236-9933. If you still have questions, contact your healthcare provider. Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 ©AstraZeneca 2025 This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: 12/2025

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 0310-9400-01 Rx only WAINUA™ 45 mg/0.8 mL (eplontersen) injection for subcutaneous use Each WAINUA autoinjector contains 45 mg eplontersen (equivalent to 47 mg eplontersen sodium) in 0.8 mL of solution, for single-dose only. Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton protected from light. Do not freeze. Do not expose to heat. 1 single-dose autoinjector IONIS™ AstraZeneca

Package/Label Display Panel

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

NDC 0310-9420-01 Rx only WAINUA™ 45 mg/0.8 mL (eplontersen) injection for subcutaneous use Each WAINUA prefilled syringe contains 45 mg eplontersen (equivalent to 47 mg eplontersen sodium) in 0.8 mL of solution, for single-dose only. Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton protected from light. Do not freeze. Do not expose to heat. 1 single-dose prefilled syringe IONIS™ AstraZeneca