Wainua

Wainua (eplontersen) is a prescription medicine used to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN or ATTRv-PN) in adults. This is a rare, progressive disease that can be fatal if not treated.

Amyloidosis is a disease caused by a buildup of abnormal proteins called amyloid in tissues and organs.

Wainua works by decreasing the amount of TTR protein made in the liver, which slows the progression of nerve damage and improves quality of life.

Wainua belongs to a class of medicines called transthyretin-directed antisense oligonucleotides. It binds to TTR mRNA and causes it to break down. This lowers the amount of both mutant and normal (wild-type) TTR protein in the blood and reduces TTR deposits in tissues.

Wainua is given as a monthly subcutaneous injection. It can be self-administered using an autoinjector.

Wainua FDA approval was granted on December 21, 2023, to AstraZeneca to treat the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. The approval followed positive results from the phase III clinical trial NEURO-TTRansform (NCT04136184), which is also called Study 1.

ATTR amyloidosis is caused by a protein in the body called transthyretin (TTR) that changes from its normal shape and then forms fibrous clumps. These clumps of misshapen protein are deposited in various organs and nerves, which can stop them from working properly.

ATTR amyloidosis polyneuropathy (ATTR-PN) is the buildup of amyloid protein in nerves. It can cause symptoms such as loss of sensation, tingling, numbness, or pain in the hands and feet.

ATTR cardiomyopathy (ATTR-CM) is when clumps of amyloid build up in the heart tissue. This affects the heart's ability to work properly, leading to symptoms similar to heart failure and an enlarged heart.

Wainua comes in a single-dose autoinjector and 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 autoinjector the first time.
• If you or your caregiver have any questions, ask your healthcare provider.
• Remove the autoinjector from the refrigerator 30 minutes before the injection and allow it to warm to room temperature. Do not use other warming methods.
• Wainua is injected under the skin (subcutaneously) in your stomach area (abdomen) or the front of your upper legs (thighs).
• A caregiver or healthcare provider may also inject Wainua into the back of your upper arm.
• Change (rotate) the injection site each time.
• Follow your healthcare provider's instructions on when to inject Wainua.
• Inject Wainua 1 time on the same day of each month.
• If you miss a dose, inject 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 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 prefilled syringe.

Pregnancy

Tell your healthcare provider if you are pregnant, plan to become pregnant, or think you may be pregnant. It is not known if Wainua can harm your unborn baby. Changes in vitamin A levels and vitamin A supplementation related to the use of Wainua may harm your unborn baby.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Wainua passes into your breast milk or can harm your baby. Talk with your healthcare provider about the best way to feed your baby while you are using this medicine.

Wainua side effects included decreased vitamin A levels (15%), vomiting (9%), protein in your urine (8%), injection site reactions (7%), blurred vision (6%), and cataracts (6%) in the clinical trial Study 1 (NEURO-TTRansform).

Low vitamin A levels are common with this medicine. 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 this medicine, your healthcare provider should refer you to an eye doctor.

Atrioventricular (AV) heart block is a serious side effect that occurred in 2% of patients in clinical trials.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Recommended Wainua dose: 45 mg given by subcutaneous injection once a month.

Wainua is available as:

• 45 mg/0.8 mL single-dose autoinjector (for use by patients or caregivers)
• 45 mg/0.8 mL single-dose prefilled syringe (for use by a healthcare provider only)

In a clinical trial of adults with hATTR polyneuropathy, Wainua lowered levels of TTR, the protein that causes the disease, by about 81% after 35 weeks. Nerve damage scores stayed about the same with Wainua but worsened in a placebo group, and quality of life improved.

These results come from the global, open-label, randomized Phase 3 NEURO-TTRansform trial in adults with ATTR amyloidosis polyneuropathy (ATTRv-PN). Wainua reduced serum transthyretin (TTR) levels by about 81% from baseline at week 35, which shows that eplontersen reduced TTR protein production.

To measure effects on nerve damage and quality of life, results were compared with a placebo group from an earlier study. At week 35, Wainua had a statistically significant effect on the modified Neuropathy Impairment Score +7 (mNIS+7), a measure of how neuropathy progresses. Scores stayed about the same in patients treated with Wainua but worsened in the placebo group.

Treatment also significantly improved patient-reported quality of life compared with the placebo group, as measured by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).

Eplontersen was also studied in ATTR cardiomyopathy (ATTR-CM) in the Phase 3 C

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Tell your healthcare provider if you take:

• Vitamin A or beta-carotene supplements.

Ask your healthcare provider or pharmacist if you are not sure whether you take any of these. Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine. Not all possible interactions are listed here.

Review the Wainua Package Insert for more detailed information about this medicine. The Wainua PI contains more detailed information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interactions, and more. Discuss any medical questions you have with your doctor or other healthcare provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called the Wainua Prescribing Information (PI) or Wainua FDA label.

• Store in the refrigerator between 36°F and 46°F (2°C to 8°C) in the original carton.
• It can also be kept at room temperature up to 86°F (30°C) in the original carton for up to 6 weeks.
• Do not let the medicine reach temperatures above 86°F (30°C).
• If you do not use an autoinjector kept at room temperature within 6 weeks, throw it away.
• Do not freeze.
• Do not expose this medicine to heat or light.

Wainua is distributed by AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850. It was developed by AstraZeneca and Ionis Pharmaceuticals, Inc.

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.