Amvuttra

Amvuttra is used to treat the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) and the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults. For ATTR-CM, Amvuttra is used to reduce death from cardiovascular causes, cardiovascular hospitalizations, and urgent heart failure visits.

It is given as a subcutaneous (under the skin) injection once every 3 months by a healthcare provider.

Amvuttra (vutrisiran) gained FDA approval on June 13, 2022, for hATTR-PN, and was approved for ATTR-CM in March 2025. There is no generic.

Amvuttra at a glance

Amvuttra works by lowering the production of a protein called TTR (transthyretin). In transthyretin-mediated amyloidosis, TTR proteins misfold and build up as toxic amyloid deposits in nerves, the heart, and other organs.

Amvuttra (vutrisiran) is an RNA interference (RNAi) therapy. It contains a small piece of genetic material (siRNA) attached to a sugar molecule that targets liver cells, where most TTR is made. Inside these cells, it breaks down the instructions for making TTR, which lowers the amount of TTR in the blood and reduces amyloid deposits in tissues.

Polyneuropathy (HELIOS-A)

In the HELIOS-A trial in people with hATTR-PN, the main measure was the change in the modified Neuropathy Impairment Score +7 (mNIS+7), a measure of nerve function in which a lower score means better function. At Month 9, nerve function improved slightly with Amvuttra (an average change of about -2.2 points) while it worsened with placebo (about +14.8 points), a difference of about 17 points in favor of Amvuttra (p less than 0.001). Quality of life, measured by the Norfolk QoL-DN score, also improved with Amvuttra compared with placebo. Treatment continued through 18 months in the trial.

Cardiomyopathy (HELIOS-B)

In the HELIOS-B trial in people with ATTR-CM, Amvuttra reduced the risk of death from any cause and recurrent cardiovascular events (cardiovascular hospitalizations and urgent heart failure visits) by about 28% compared with placebo over up to 36 months. In people who were not also taking tafamidis, the risk was reduced by about 33%.

Amvuttra is given by a healthcare provider as a subcutaneous (under the skin) injection.

• It is given once every 3 months (4 times a year).
• It can be injected into the abdomen (but not within 2 inches of the belly button), the thighs, or the back of the upper arms.
• If the syringe has been refrigerated, it is allowed to warm to room temperature for about 30 minutes before injection.
• Tell your care team if you feel any burning, pain, or swelling where Amvuttra is injected.

Your doctor may have you take a vitamin A supplement while using Amvuttra. Take only the amount prescribed, and call your doctor right away if you have vision problems, especially at night.

What happens if I miss a dose?

If you miss your appointment, contact your healthcare provider as soon as possible to have Amvuttra given as soon as you can. After that, receive the next dose 3 months after the most recently given dose.

There are no contraindications to Amvuttra. Before receiving it, tell your doctor about all your medical conditions and allergies and especially if you are:

• pregnant or intending to become pregnant
• breastfeeding.

Pregnancy

Amvuttra may harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. Because Amvuttra lowers vitamin A levels, and both too little and too much vitamin A can cause vision problems, central nervous system defects, and other serious effects in an unborn baby, your doctor will guide your vitamin A intake. If you become pregnant, your name may be listed on a pregnancy registry that tracks the effects of Amvuttra.

Breastfeeding

It may not be safe to breastfeed while using Amvuttra. Ask your doctor about any risks.

Common side effects

The most common side effects of Amvuttra are:

• pain in the arms or legs (pain in the extremities)
• joint pain (arthralgia)
• shortness of breath
• low vitamin A levels
• injection site reactions, such as pain, swelling, redness, bruising, or itching (usually mild and short-lived).

Serious side effects and warnings

Amvuttra may cause the following serious side effects:

• Low vitamin A levels. Amvuttra lowers the amount of vitamin A in your blood. Your doctor will tell you to take a vitamin A supplement at the recommended daily allowance. Do not take more vitamin A than your doctor recommends, because higher doses do not help and serum vitamin A levels do not reflect the total vitamin A in the body. If you have vision problems such as night blindness, tell your doctor, who may refer you to an eye specialist.
• Harm to an unborn baby. Amvuttra lowers vitamin A levels, and too much or too little vitamin A can harm an unborn baby. Tell your healthcare provider if you are pregnant, plan to become pregnant, or become pregnant during treatment.

In clinical trials, a small number of people had serious heart rhythm problems (atrioventricular heart block). Amvuttra is for adults only; it is not known if it is safe and effective in children.

This is not a complete list of side effects. Call your doctor for medical advice about side effects. You may report side effects to Alnylam Pharmaceuticals at 1-877-256-9526 or to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Dose of Amvuttra for hATTR-PN or ATTR-CM

• 25 mg administered by subcutaneous injection once every 3 months.

Tell your doctor about all your current medicines and any medicine you start or stop, including prescription and over-the-counter medicines, vitamins, and herbal products.

No formal drug interaction studies have been done with Amvuttra, but it is not expected to cause interactions with other medicines or to be affected by medicines that inhibit or induce cytochrome P450 (CYP) enzymes.

Does Amvuttra interact with my other drugs?

Enter medications to view a detailed interaction report using our Drug Interaction Checker.

• Store in the original carton at 36 to 86 degrees Fahrenheit (2 to 30 degrees Celsius) until ready to use.
• Do not freeze.
• If stored cold, allow the syringe to reach room temperature for about 30 minutes before use.

Active ingredient: vutrisiran 25 mg in 0.5 mL.

Inactive ingredients: water, sodium hydroxide, phosphoric acid, sodium phosphate monobasic dihydrate, sodium phosphate dibasic dihydrate, and sodium chloride. The prefilled syringe is not made with natural rubber latex.