When you’re living with a rare condition like hereditary ATTR (hATTR) amyloidosis, the last thing you need is confusion about your treatment options. Two medications — Onpattro (a formulation of patisiran) and Amvuttra (a formulation of vutrisiran) — may sound alike, but understanding their important differences can help you feel more informed and empowered during treatment conversations.

Both medications treat hATTR amyloidosis and work in similar ways by reducing the buildup of abnormal transthyretin (TTR) protein. However, they differ in several ways — including how they’re given, how often they’re needed, and their potential side effects.

Read on to learn about these seven key differences, explained clearly and simply. Remember, this information is not a substitute for personalized medical advice. Your amyloidosis specialist — who knows the details of your diagnosis and health history — can help guide decisions that are best for you. Use this overview as a starting point for confident, informed conversations with your doctor.

Ways Onpattro and Amvuttra Are Alike

Onpattro and Amvuttra are medications used to treat nerve symptoms caused by hATTR amyloidosis. This is a rare, inherited condition in which a protein called transthyretin builds up in the nerves, heart, and other organs. Over time, this protein buildup can damage tissues — including nerves — leading to symptoms like tingling, weakness, or nerve pain in the hands and feet. These symptoms of nerve damage are collectively referred to as neuropathy. When neuropathy occurs in several different areas, it’s known as polyneuropathy.

Both drugs belong to a class of treatments known as RNA interference (RNAi) therapies. These treatments work by blocking the production of abnormal TTR protein before it can build up and cause harm. Think of it like turning off a faucet to stop a leak instead of mopping up a spill — RNAi therapies target the source.

Onpattro and Amvuttra are also considered disease-modifying therapies, not just treatments for symptoms. That means they’re designed to help slow or stop disease progression. In clinical trials, many people taking either drug experienced slower worsening of nerve problems — and in some cases, improvements in daily activities.

So far, no major differences in effectiveness have been found between the two drugs. Both help reduce nerve damage and support quality of life for people living with hATTR amyloidosis.

So, how do you choose — or how do doctors decide which one to recommend? Let’s look at the key differences next.

1. Amvuttra Is Taken Less Frequently Than Onpattro

One of the biggest practical differences between these two treatments is how often they’re needed.

• Onpattro is typically given once every three weeks.
• Amvuttra is typically given once every three months.

That means Amvuttra requires only four doses per year, compared to 17 or more doses for Onpattro. For people who have mobility challenges, busy work schedules, or long travel times to infusion centers, Amvuttra may be easier to fit into daily life.

That said, some people may appreciate the regular in-person check-ins that come with Onpattro infusions — especially when starting treatment or when close monitoring feels reassuring. Choosing between the two often comes down to your lifestyle, preferences, and what feels manageable for you.

2. Onpattro Is an IV Infusion, While Amvuttra Is a Shot Under the Skin

Another key difference is how each medication is given.

• Onpattro is delivered through an intravenous (IV) infusion, which must be done under medical supervision — typically at a clinic or infusion center.
• Amvuttra is given as a subcutaneous injection, which is a quick shot under the skin. In some cases, it can be done at home by a nurse, trained caregiver, or even the person receiving treatment.

IV infusions usually take longer and may require a clinic visit, time off work, and pretreatment medications to help prevent side effects. In contrast, Amvuttra’s injection is often quicker and more convenient — especially for people who prefer to avoid IVs or have difficulty getting to a clinic.

For many people, the drug-administration method can be one of the most important factors in choosing a treatment.

3. Amvuttra May Cause Fewer Infusion Reactions Than Onpattro

Because Onpattro is given as an IV infusion and takes longer to administer, it may cause infusion-related side effects. These can include:

• Fever or chills
• Shortness of breath
• Discoloration or swelling
• Dizziness

To help prevent these side effects, people are usually given premedications before each Onpattro infusion. These may include steroids and antihistamines, which can have their own side effects.

Amvuttra, which is given as a shot under the skin, is generally less likely to cause these types of reactions. Some people may experience mild skin discoloration, swelling, or tenderness at the injection site, but serious side effects are uncommon.

For people who’ve had difficulty with infusion reactions in the past, Amvuttra may feel like a simpler or more comfortable option.

4. Onpattro Has Been Around Longer Than Amvuttra

Onpattro was the first RNAi therapy approved by the U.S. Food and Drug Administration (FDA). It became available in 2018 and has since been used by a larger number of people. As a result, it has more long-term safety data available and a longer track record in clinical practice.

Amvuttra, approved in 2022, is newer. It uses the same core approach to treatment — targeting and reducing production of abnormal transthyretin (TTR) protein — but with differences like less frequent dosing.

Early clinical trial results for Amvuttra have been encouraging, and ongoing studies show similar or, in some cases, improved outcomes on certain measures. Still, some doctors may feel more confident starting with Onpattro, especially for people who are at higher risk or who prefer a treatment that’s been used for more years.

5. Doctors May Recommend One Over the Other

There’s no official guideline saying which drug should be used first, but doctors often make personalized recommendations based on each person’s needs and circumstances.

For example, someone who travels frequently or lives far from an infusion center may prefer Amvuttra’s less frequent dosing schedule. On the other hand, a person who’s already doing well on Onpattro may choose to stay on it rather than switch.

Doctors also may consider:

• Other health conditions
• History of allergic reactions or infusion side effects
• A person’s comfort with IV infusions versus injections
• Insurance coverage or cost assistance programs
• Dosing schedule preferences

Some specialists may lean toward Amvuttra for newly diagnosed individuals because of its convenience and lack of required premedications, but most decisions are made case by case, in partnership with the person receiving treatment.

6. Neither Drug Is Currently Approved for Children

As of April 2025, both Onpattro and Amvuttra are FDA-approved only for treating polyneuropathy caused by hATTR amyloidosis in adults. This means that neither medication is currently approved for use in children or teens.

If you care for a child, teen, or young adult with a family history of hATTR amyloidosis, talk with your doctor about when to consider genetic testing and how to start monitoring for early signs of the condition — even if treatment isn’t needed right away. Knowing what to watch for can help support earlier diagnosis and better outcomes.

7. Costs and Insurance Coverage May Differ

The cost of both medications can be high, but what you actually pay out of pocket depends on your insurance plan. Factors that can affect coverage include:

• Prior authorization requirements
• Specialty pharmacy restrictions
• Availability of copay or patient assistance programs
• Whether you’re covered by Medicare or a commercial insurance plan

Amvuttra may reduce total costs in some situations, since it’s given less frequently and doesn’t require premedications or time spent at an infusion clinic. However, insurance coverage varies, and some insurers may have existing systems or contracts in place that make Onpattro the preferred option.

To understand what’s financially practical for you, always talk with your healthcare provider and any available financial support programs. They can help you navigate your insurance benefits and find the most affordable treatment path.

Ask Questions and Stay Informed

Onpattro and Amvuttra are both important advances in the treatment of hATTR amyloidosis. Unlike many older treatments, these therapies address the root cause of the condition, not just the symptoms. They offer real hope for people living with this rare disease.

Choosing between the two isn’t about picking a “better” drug — it’s about finding the option that works best for you medically, practically, and financially. The right choice may depend on your daily routine, travel needs, preferences around IV infusions versus injections, and your neurology team’s experience with each medication.

Be open with your care team. Ask about side effects, monitoring needs, insurance coverage, and what to expect over time. Don’t hesitate to request written materials or resources, and consider connecting with others who are navigating hATTR amyloidosis, too. Many people with this condition are willing to share what they’ve learned — and you don’t have to figure this out alone.

Talk With Others Who Understand

On MyAmyloidosisTeam, the social network for people with amyloidosis and their loved ones, more than 2,700 members come together to ask questions, give advice, and share their stories with others who understand life with amyloidosis.

Have you used Onpattro, Amvuttra, or both for polyneuropathy? Share your experience in the comments below, or start a conversation by posting on your Activities page.