Vyndamax for Transthyretin Amyloid Cardiomyopathy

Medically Reviewed by Beth Johnston, PharmD, BCPS on August 21, 2024
7 min read

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a type of amyloidosis, which is a group of diseases where abnormal proteins (amyloids) build up and affect areas of the body. ATTR-CM is a long-term, progressive heart condition where the amyloids build up in the heart. This makes it harder for the heart to function properly.  

Vyndamax was the first once-daily medicine for ATTR-CM that helps slow the progression of the disease and improve your quality of life.

There are two types of ATTR-CM (see table below). In both types, there is a buildup of a protein called transthyretin (TTR). TTR protein is made in the liver, brain, and retina of the eye. It helps to carry a thyroid hormone (thyroxine) and vitamin A (retinol) around the body. In ATTR-CM, the TTR protein is weak and unstable. This causes the protein to build up in the heart and other organs. The heart muscle becomes thick and stiffens, which leads to heart failure

ATTR-CM

Details

Symptoms

Wild-type 

(wtATTR)

  • Also called senile systemic amyloidosis
  • Occurs in older people due to age-related changes to the TTR protein
  • More commonly seen in White men over 60

 

Heart Failure Symptoms

  • Unusual tiredness (fatigue)
  • Shortness of breath or difficulty breathing
  • Swelling of feet, ankles, or legs
  • Unusually fast weight gain

 

Other Symptoms

  • Numbness, tingling or pain in your fingers, lower back, feet, or toes
  • Diarrhea or constipation
  • Nausea or feeling full quickly

Hereditary 

(hATTR)

  • Caused by a change (mutation) in your TTR gene
  • Hereditary means that the abnormal gene can be passed down from a close family member 
  • Most common mutation (V122I) is found almost always in Black people
  • Can affect other organs in the body besides the heart

Your health care provider will focus on treating your symptoms and recommend lifestyle changes for diet and exercise. Until the approval of Vyndamax, there was only symptom management or heart or liver transplants. Now, there are new medicines that reduce the amount of abnormal TTR proteins. Vyndamax contains tafamidis, which was the first active ingredient developed for ATTR-CM. Vyndamax helps to stabilize the TTR protein. This reduces the buildup of the protein and slows the progression of the disease. 

One study was done to see if tafamidis, the active ingredient in Vyndamax, was safe and effective for ATTR-CM compared with placebo. Placebo-controlled studies help researchers see differences in benefit or harm of a medicine when compared with no treatment. People took either 20 milligrams, 80 milligrams, or a placebo once daily for 30 months. 

All people in the study had a diagnosis of wild-type (76%) or hereditary (24%) ATTR-CM based on a biopsy. People in the study were at least 18 years old, with an average age of 74. Most of the people in the study identified as White (80%), with 14% identifying as Black, 5% as Asian, and 1% as Other. A little more than half of the people had class II heart failure, which is moderate disease with limitations of physical activity.

Each person in the study had heart involvement based on the following signs:

  • Thickening heart muscle based on the thickness being greater than 12 millimeters seen on echocardiogram
  • A history of heart failure, with at least one hospitalization due to heart failure or specific treatment to help with signs or symptoms of heart failure
  • A high level ( ≥ 600 pg/mL) of N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is protein in the body that goes up when your heart is working harder than it should
  • A 6-minute walking test (6MWT) with a distance more than 100 meters (approximately 330 feet), which measures physical ability

Effectiveness was measured by checking how many people died from any reasons during the study, called “all-cause mortality,” and how many people had a hospital stay for heart-related problems at the end of 30 months. The goal was to see if people taking tafamidis lived longer or needed fewer hospitalizations compared to people taking placebo. Other measures included changes in the 6MWT and the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS), which looks at quality of life. 

Tafamidis was shown to reduce the all-cause mortality and heart-related hospitalizations when compared to placebo after 30 months of treatment. 

All-cause mortality. People who took tafamidis were more likely to be alive or didn’t require heart or lung transplant at 30 months (71%) compared with people who took placebo (57%). This shows that tafamidis may play a role in slowing the progression of your ATTR-CM. 

Heart-related hospitalizations. People taking tafamidis went to the hospital about 0.48 times per year for heart problems, while those taking the placebo went about 0.70 times per year. This means that people taking tafamidis went to the hospital less often than those taking the placebo. In fact, the risk of needing to go to the hospital was about 32% lower for people taking tafamidis.

6MWT and KCCQ-OS. The 6MWT and KCCQ-OS are tools used to look at overall fitness, heart health, and impact of symptoms on daily activities. The study showed that people who took tafamidis did better in both tests compared with people who took placebo. On average, people who took tafamidis could walk 76 meters (250 feet) and reported feeling better, scoring 14 points higher on the questionnaire. These changes were seen as early as 6 months after treatment started. 

Your results may differ from what was seen in clinical studies. You and your health care provider should determine if the benefits outweigh any potential risks. 

After a few months, you may see improvements in the frequency or severity of your symptoms. You may see some of the following changes:

  • Less shortness of breath
  • Easier to do physical tasks, like walking or climbing stairs
  • Less trips to the hospital for heart-related reasons

Vyndamax works gradually, so you may not see quick changes in your symptoms. The long-term goal is to slow progression, so it is important to track your symptoms and review them with your health care provider. Always keep taking your medicine even if you don’t feel immediate changes in your symptoms. Your health care provider may also monitor your heart with different tests.

If you have hereditary ATTR-CM, talk to your health care provider about genetic testing for the TTR mutation. Close relatives, like siblings or adult children, could also be at risk for AATR-CM. If it is identified that you or a family member has a TTR mutation, talk to a health care provider about genetic counseling to help you understand the results and determine next steps. 

Always tell your health care provider about any prescription or over-the-counter (OTC) medicines, vaccines, vitamins/minerals, herbal products, and other supplements you are using. 

Vyndamax can affect the blood levels of certain medicines. This may increase the risk of side effects from these medications. Talk with your health care provider if you are using any of the following breast cancer-resistant protein (BCRP) substrates:

  • Anticancer medicines like gefitinib (Iressa), imatinib (Gleevec), or methotrexate (Trexall and others)
  • Cholesterol medicines like rosuvastatin (Crestor)
  • Antibiotics like ciprofloxacin (Cipro)
  • Antiviral medicines that contain lamivudine or zidovudine
  • Sulfasalazine (Azulfidine), a medicine commonly used for inflammatory bowel disease, rheumatoid arthritis, or other autoimmune diseases

This is not a complete list of medicines that may interact with Vyndamax. Tell your pharmacist or health care provider about all the prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, or other supplements you take or have recently taken. This will help them determine if there are any interactions or if you need a dosage adjustment.

Vyndamax is considered a specialty medicine, which is a high-cost medication that is taken for rare, complex, or long-term (chronic) diseases. It requires a different process than picking up your prescription at a local pharmacy. This process helps you stay on track with your treatment. Your health care provider will work with you, your insurance company, and/or the manufacturer to start the process. 

Here are some differences that you may expect. 

Insurance approval. Your insurance may require approval for using this medicine, also called prior authorization. The insurance company reviews the prescription from your health care provider to make sure it is covered and determines the process that needs to be followed. 

Specialty pharmacy. You may be required to use a specialty pharmacy to get your medicine each month. The pharmacist works with your health care provider and insurance company, helps with instructions on how to take and store the medicine, monitors side effects, and tracks refills. This pharmacy will also work with you on how to get you the medicine, either at a store or through the mail. Your health care provider will work with you and your insurance company on which pharmacy to use and the information that will be provided. 

Cost assistance. There is a co-pay assistance program from the manufacturer that may allow you to pay $0 for your prescription. Whether you are eligible depends on whether you have prescription insurance and what type of insurance you have. You can find out more at www.vyndamax.com/financial-assistance or by calling 888-222-8475.