Understanding Approved Treatments for ATTR-CM
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a condition that happens when a protein that your liver makes called transthyretin (TTR), doesn't work right. Clumps of the protein deposit within your heart's muscles.
These deposits can cause your heart's main pumping chamber – the left ventricle – to become stiff and weak. As a result, your heart has to work a lot harder to pump blood. They can also cause nerve damage, with symptoms of pain, tingling or numbness, and weakness.
ATTR is uncommon, but it can be life-threatening.
There's no cure for ATTR-CM, but certain medications can slow the disease and help you feel better. The therapy you receive may depend on the type of ATTR you have and how severe it is.
Your treatment plan may also include supportive treatments to treat your symptoms and help you have a better quality of life.
What Are the Treatments for ATTR-CM?
Treatments for ATTR-CM typically aim to stop the disease from getting worse. This helps protect your heart and other organs from further damage caused by ATTR-CM. Therapies for ATTR can also improve the symptoms you have.
The nonsteroidal anti-inflammatory (NSAID) drug diflunisal is also sometimes used "off-label" to treat ATTR-CM. This means your doctor gives you the medicine for something different than what it was approved for. Some early research suggests diflunisal may help stabilize ATTR-CM and improve survival in people with the condition.
Transthyretin (TTR) Stabilizers
What are transthyretin (TTR) stabilizers?
TTR stabilizers are drugs that help keep the TTR protein in your body stable. The medicines bind to the TTR protein to help keep it strong. This means it's less likely to fall apart and form dangerous clumps.
How effective are TTR stabilizers?
You may feel better and live longer if you take these medicines.
- In a phase III trial, patients who took acoramidis for 30 months had a 42% lower risk of death from all causes, compared to those who took a placebo.
- Results from the ATTR-ACT clinical trial showed that people with ATTR who took this medicine for 30 months had a 13% increase in survival, compared to those who took a placebo (sugar pill). The medicine was also linked to lower heart-related hospital stays. In another large review of 15 studies, scientists found that tafamidis lowered the risk of death and the need for a heart transplant in those with ATTR.
- The HELIOS-B trial for the treatment of ATTR-CM with vutrisiran found that it lowered the risk of death in those taking it from heart events by 33%, and the risk of death from all causes by 36%, compared to people in the placebo group.
How do you take TTR stabilizers?
You typically take TTR stabilizers by mouth as a pill or capsule.
- Acoramidis is taken twice a day.
- Tafamidis is taken once a day.
Are TTR stabilizers safe?
The TTR stabilizers acoramidis and tafamidis are generally considered safe, especially if you take them as your doctor prescribes.
What are the side effects of TTR stabilizers?
Acoramidis can cause mild symptoms, like belly pain or diarrhea.
In clinical studies, there were no side effects reported in patients who took tafamidis.
Who should not take TTR stabilizers?
You shouldn't use TTR stabilizers if you're pregnant or plan to become pregnant. These medicines could harm an unborn baby. You also shouldn't take them if you're breastfeeding.
How much do TTR stabilizers cost?
TTR stabilizers can be very expensive, costing several hundred thousand dollars per year. But the cost you pay out of pocket will depend on your insurance coverage, your pharmacy, and any discount programs you use.
Makers of these medications offer financial assistance programs to help you pay for these medicines. These plans may help you whether you have health insurance or not.
What are Transthyretin (TTR) RNA-Targeted Therapies?
TTR RNA-targeted therapies are medicines that turn off the instructions that tell your body to make the TTR protein. When the drugs block this process, your liver makes less TTR protein, so it doesn't build up. This can lead to fewer clumps.
How effective are TTR RNA-targeted therapies?
Studies show that TTR RNA-targeted therapies can improve your survival outlook and lessen side effects. Specifically, patisiran is designed to help ATTR patients with polyneuropathy (nerve damage).
- Patients who took patisiran had improvements in polyneuropathy symptoms, quality of life, walking, nutrition, and daily activities. It also lowered TTR levels by 84% after 18 months.
- Vutrisiran (Amvuttra) has been shown to improve nerve function and lessen the risk of heart events. In a phase III clinical trial, the drug also lowered patients' risk of death from any cause by 36%, compared to a placebo. It reduced heart failure hospitalizations by 33% and urgent heart failure visits by 46% over 36 months.
How do you take TTR RNA-targeted therapies?
You get TTR RNA-targeted therapies as infusions or injections, depending on the drug:
- Patisiran as a drip into a vein, once every three weeks
- Vutrisiran as an injection under the skin, once every three months
Are TTR RNA-targeted therapies safe?
TTR RNA-targeted therapies are generally safe, but each may pose some possible risks.
- Patisiran can trigger serious infusion-related reactions. For this reason, a health care professional will need to watch your health closely during your infusions. The medicine can also lower the amount of vitamin A in your blood, which can lead to vision problems. You will need to take a daily supplement.
- Vutrisiran (Amvuttra) may also cause low levels of vitamin A, which requires you to take a supplement.
What are the side effects of TTR RNA-targeted therapies?
TTR RNA-targeted therapies can cause side effects.
The most common symptoms linked to patisiran use are:
- Respiratory infections, like colds, sinus infections, and nasal congestion
- Infusion reactions, like flushing, nausea, tummy pain, back pain, breathing issues, or headache
Vutrisiran (Amvuttra) can commonly cause these issues:
- Pain, especially joint pain
- Shortness of breath
- Low levels of vitamin A
Who should not take TTR RNA-targeted therapies?
It's not known if TTR RNA-targeted therapies could affect an unborn baby. You should talk to your doctor if you're pregnant or plan to become pregnant before you take these medicines. The same goes for breastfeeding.
Also, steer clear of these meds if you've had an allergic reaction to them before.
How much do TTR RNA-targeted therapies cost?
TTR RNA-targeted drugs are expensive, with retail prices of hundreds of thousands of dollars per year.
Drugmakers offer patient assistance programs to help you afford these medicines. You may be able to get them at reduced prices if you qualify.
5 Things to Keep in Mind When Considering Targeted Medications for ATTR-CM
When deciding on a medicine for ATTR-CM, talk to your doctor about your treatment goals and the benefits and risks of each drug. Here are five important things to ask about.
- Cost
Both TTR stabilizers and TTR RNA-targeted therapies are expensive. Check out what your health insurance plan will cover. You may want to look at what patient assistance programs you qualify for before you decide on which drug to use.
- Your type of ATTR
Your treatment options may depend on the type of ATTR you have. For example, these medicines can be used to treat both hereditary and wild-type ATTR:
- Acoramidis
- Tafamidis
- Vutrisiran
Drugs that are designed to treat polyneuropathy caused by hereditary ATTR (only) include:
- Patisiran
- Side effects
It's important to think about the side effects of these medicines. Some, like tafamidis, cause very few issues. But others may trigger severe symptoms.
- Delivery method
While you take TTR stabilizers by mouth daily, you get TTR RNA-targeted therapies as injections. You'll need to think about which option fits your needs and lifestyle best.
- Your treatment goals
Some medicines for ATTR target specific symptoms. For example, acoramidis, tafamidis, tafamidis meglumine, and vutrisiran are designed to reduce heart-related deaths and hospital visits for people with cardiomyopathy (ATTR-CM). Patisiran specifically treats symptoms of polyneuropathy (ATTR-PN).
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