Eplontersen

Eplontersen is used for polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN or ATTRv-PN), which 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. Eplontersen works by decreasing the amount of TTR protein that is made, which slows disease progression and improves neuropathy and the patient's quality of life. Eplontersen brand name is Wainua.

Eplontersen drug class of medications called LICA (ligand-conjugated antisense oligonucleotide). Eplontersen mechanism of action is by causing the breakdown of mutant and wild-type TTR mRNA by binding to the TTR mRNA, which lowers serum TTR protein and TTR protein deposits in tissues.

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

Eplontersen FDA approval was received for the indication polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, on December 21, 2023. FDA approval was granted to eplontersen (Wainua brand) for the company AstraZeneca after positive results from the phase III eplontersen clinical trial NEURO-TTRansform (NCT04136184).

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 then deposited into various organs and nerves, which can stop the organs and nerves from working properly.

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

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

Eplontersen 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 eplontersen single-dose autoinjector.
• Your healthcare provider will show you or your caregiver how to inject eplontersen using the single-dose autoinjector the first time.
• If you or your caregiver has any questions, ask your healthcare provider.
• Remove the single-dose autoinjector from the refrigerator 30 minutes before the injection and allow it to warm to room temperature. Do not use other warming methods.
• Eplontersen 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 eplontersen in the outer area of your upper arm.
• Follow your healthcare provider's instructions on when to inject eplontersen.
• Eplontersen 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 eplontersen 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 eplontersen using the single-dose prefilled syringe.

Pregnancy

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

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if eplontersen 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 this medicine.

Common eplontersen side effects were low vitamin A serum levels and vomiting, which occurred in at least 9% of patients. Low vitamin A level is a serious, but common side effect of treatment with this medicine. Your healthcare provider should tell you to take vitamin A supplements while using eplontersen. 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 this medicine, your healthcare provider should send you to see an eye doctor.

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 eplontersen dose: 45 mg administered by subcutaneous injection once a month.

Eplontersen is available as a 45 mg/0.8 mL single-dose autoinjector.

In the global, open-label, randomized Phase 3 NEURO-TTRansform trial for eplontersen in patients with ATTR amyloidosis polyneuropathy (ATTRv-PN), there was an 81.2% reduction in serum transthyretin (TTR) concentration when compared to the baseline, showing that eplontersen reduced TTR protein production.

The study showed that eplontersen had a statistically significant effect on the modified Neuropathy Impairment Score +7 (mNIS+7), which is a measure of neuropathic disease progression when compared to the placebo group.

Treatment also significantly improved patient-reported quality of life compared to the external placebo group (p<0.0001) as measured by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).

Eplontersen is also being studied in the treatment of ATTR cardiomyopathy (ATTR-CM).

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 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. Not all possible interactions are listed here.

Review the eplontersen prescribing information (Wainua prescribing information) for more detailed information about this medicine. The Eplontersen prescribing information (PI) contains more detail information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction and more. Discuss any medical questions you have with your doctor or other health care 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 prescribing information is sometimes called eplontersen Package Insert or eplontersen FDA label.

• Store in the refrigerator between 36°F to 46°F (2°C to 8°C) in the original carton.
• This medicine 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 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 to heat or light.

Wainui (Eplontersen) by AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850 AstraZeneca.

Ionis Pharmaceuticals, Inc.

Active ingredient: eplontersen sodium.

Wainua 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.