Amvuttra, Onpattro, Tegsedi, and More: 6 Medications for Hereditary ATTR
Key takeaways:
Hereditary transthyretin amyloidosis (hATTR) is a rare, inherited health condition. It can cause problems in various organs, such as the heart, liver, kidneys, and nerves.
Amvuttra (vutrisiran), Onpattro (patisiran), and Tegsedi (inotersen) are FDA approved to treat nerve damage in adults with hATTR. Vyndamax (tafamidis) and Vyndaqel (tafamidis) treat cardiomyopathy (heart muscle disease). Diflunisal is taken off-label for nerve damage.
The best hATTR medication for you depends on your symptoms and personal preferences. Talk with your healthcare provider to learn about different treatment options for you.
Table of contents
Hereditary transthyretin amyloidosis (hATTR) is a rare health condition. If you’re born with it, a change in your genes can cause abnormal amyloid proteins to build up in different parts of your body. These amyloid deposits cause problems in the heart, liver, kidneys, and nerves.
There is no cure for hATTR. A liver transplant used to be the only option for managing hATTR. That’s because the transthyretin (TTR) proteins are made in the liver. But with advances in medical research, there are now six prescription medications that can help slow hATTR symptoms and prevent them from worsening.
How do hATTR treatments work?
Medications for hATTR work in slightly different ways, but they have the same goal: to reduce the amount of misfolded amyloid protein in your body.
Save over 40% on Qsymia with GoodRx
Discover the once daily Qsymia for weight management. Qsymia is for adults and children 12-17 in combination with a healthy diet and regular exercise.
The first three medications in this list are known as “gene silencers.” They act on genes to lower the amount of TTR protein made in the liver. Currently, they’re approved to treat nerve symptoms of hATTR. They may be approved to treat people with heart amyloid symptoms in the future.
The next two are “protein stabilizers.” They act on TTR proteins to stop them from folding and causing amyloid deposits. They’re approved to treat a specific type of heart disease caused by amyloid deposits (hATTR cardiomyopathy).
The last is a nonsteroidal anti-inflammatory drug (NSAID) that’s sometimes taken off-label — meaning not FDA approved for this use — as a protein stabilizer.
We review these three types of medications (six medications in all) in more detail below.
1. Amvuttra
Approved in 2022, Amvuttra (vutrisiran) is the newest treatment option for hATTR. It’s approved to manage nerve problems in adults with hATTR, helping manage symptoms such as difficulty walking and numbness in the hands and feet. It comes as an injection that’s given under the skin once every 3 months by a healthcare provider.
Amvuttra belongs to a group of medications called small interfering ribonucleic acids (siRNAs). It works by lowering the amount of transthyretin (TTR) protein made in the liver.
This mechanism appears to be effective for many people. A phase 3 study showed about 50% of people receiving Amvuttra had nerve function improvements after 9 months of consistent use.
Good to know: Amvuttra can lower your vitamin A levels — an essential component of eye health. Your healthcare provider may ask you to take a vitamin A supplement while you’re receiving Amvuttra.
2. Onpattro
Like Amvuttra, Onpattro (patisiran) is a siRNA medication that’s approved to manage nerve problems from hATTR in adults. Onpattro is given as an intravenous (IV) infusion every 3 weeks in a medical setting. Each infusion takes about 1 hour and 20 minutes.
In a phase 3 study, conducted over a 1.5-year period, Onpattro improved nerve symptoms in about 56% of people. Onpattro also improved quality of life in about 51% of people.
However, Onpattro infusions can cause infusion reactions. Symptoms may include redness, swelling, and shortness of breath. About 60 minutes before your infusion, your healthcare provider will administer several medications to prevent symptoms, such as:
Acetaminophen (Tylenol)
An IV corticosteroid, such as dexamethasone
A histamine-1 blocker antihistamine, such as diphenhydramine (Benadryl)
A histamine-2 blocker antihistamine, such as famotidine (Pepcid AC)
Good to know: Onpattro may also lower your vitamin A levels. It may be a good idea to take a supplement to prevent vision problems. Your healthcare provider can help you select a vitamin A supplement that’s right for you, if applicable.
3. Tegsedi
Like Amvuttra and Onpattro, Tegsedi (inotersen) is approved to treat nerve problems in adults with hATTR. Like the first two treatments, it’s a “gene silencer,” but it’s a different type of gene silencer, called an antisense oligonucleotide.
Research shows Tegsedi is effective at helping improve nerve-related symptoms and quality of life. And one convenient feature of Tegsedi is that you can administer it yourself. Tegsedi is a once-weekly under-the-skin injection. Your pharmacist can teach you how to give yourself a Tegsedi injection.
Keep in mind though that it carries a boxed warning — the FDA’s most serious type of warning — about the risk of bleeding and kidney problems. For this reason, Tegsedi is only available through a restricted Risk Evaluation and Mitigation Strategy (REMS) medication safety program. You’ll need to enroll in the program and agree to participate in weekly blood tests and biweekly urine checks.
Good to know: Tegsedi interacts with medications that raise the risk of bleeding. NSAIDs, such as ibuprofen (Motrin, Advil) and blood thinners, such as warfarin (Coumadin, Jantoven), are a couple of examples. Keep a current list of your prescription and over-the-counter medications handy. This can help your pharmacist and healthcare provider screen for any interactions.
4. Vyndamax
Vyndamax is one of two medications containing the active ingredient tafamidis. It is a type of hATTR medication called a TTR stabilizer. It’s approved to manage cardiomyopathy (heart muscle disease) in adults with hATTR.
Research shows Vyndamax lowers the risk of hospitalization and death caused by heart problems.
This medication is available as a 61 mg capsule. One unique perk of Vyndamax is that you can take only one capsule once a day. The recommended dose is 61 mg (1 capsule) by mouth once daily.
5. Vyndaqel
Vyndaqel is the other hATTR medication that contains tafamidis. It’s also approved to treat cardiomyopathy in adults with hATTR. Like Vyndamax, Vyndaqel lowers the risk of hospitalization and death from heart problems.
But Vyndaqel and Vyndamax aren’t exactly the same. Their doses are different, and you can’t substitute one for the other because of how they’re made. Vyndaqel comes as 20 mg capsules. The typical dose is 80 mg (4 capsules) by mouth once daily.
6. Diflunisal
The last medication is diflunisal, a NSAID that can be used off-label for adults with hATTR.
As with Vyndamax and Vyndaqel, it’s considered a TTR stabilizer. In fact, its chemical structure is similar to tafamidis. Some studies suggest that this oral tablet is effective for treating nerve damage in adults with hATTR. It may potentially treat cardiomyopathy, too. Other benefits of this treatment are its availability and affordability.
The typical dose for hATTR is 250 mg by mouth twice a day. But it can come with some side effects, such as fluid retention and stomach upset.
How to choose the best hereditary ATTR medication
Choosing the best hATTR medication depends on different factors, such as what symptoms you’re treating, your personal preferences, and your insurance coverage status. Interactions may play into your decision, too.
That being said, Amvuttra, Onpattro, or Tegsedi are go-to medications if you’re experiencing nerve-related symptoms. But if you have cardiomyopathy and are looking for a once a day oral medication, Vyndamax or Vyndaqel could be a good choice. Talk with your healthcare provider about which medication is right for you.
The bottom line
There are currently five FDA-approved medications to manage and slow down symptoms of hereditary transthyretin amyloidosis (hATTR). Amvuttra (vutrisiran), Onpattro (patisiran), and Tegsedi (inotersen) are injectable medications that manage nerve problems. Vyndamax (tafamidis) and Vyndaqel (tafamidis) are oral medications that treat cardiomyopathy. Diflunisal is an off-label option for managing nerve damage. Your healthcare provider can recommend the best treatment based on your symptoms and situation.
Why trust our experts?
References
Adams, D., et al. (2018). Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. The New England Journal of Medicine.
Adams, D., et al. (2022). Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: A randomized clinical trial. Amyloid.
Akcea Therapeutics. (n.d.). Tegsedi REMS (risk evaluation and mitigation strategy) program.
Akcea Therapeutics, Inc. (2023). Tegsedi [package insert].
Alnylam Pharmaceuticals, Inc. (2022). Alnylam announces FDA approval of amvuttra (vutrisiran), an RNAi therapeutic for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
Alnylam Pharmaceuticals, Inc. (2023). Amvuttra [package insert].
Alnylam Pharmaceuticals, Inc. (2023). Onpattro [package insert].
American Heart Association. (2022). What is hATTR amyloidosis?
Amyloidosis Research Consortium. (n.d.). Treatment overview: Hereditary transthyretin amyloidosis.
Benson, M. D., et al. (2018). Inotersen treatment for patients with hereditary transthyretin amyloidosis. The New England Journal of Medicine.
Maurer, M. S., et al. (2018). Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. The New England Journal of Medicine.
MedlinePlus. (2022). Tafamidis.
Pfizer. (2019). U.S. FDA approves vyndaqel and vyndamax for use in patients with transthyretin amyloid cardiomyopathy, a rare and fatal disease.
Pfizer Laboratories Div Pfizer Inc. (2023). Vyndaqel: Vyndamax [package insert].
Sekijima, Y., et al. (2015). Safety and efficacy of long-term diflunisal administration in hereditary transthyretin (ATTR) amyloidosis. Amyloid.