Amyloidosis is a condition where a protein called amyloid builds up in your organs and tissues. It can be hereditary, meaning it is passed down in families due to broken genes, or it can happen naturally due to aging. Amyloidosis can lead to organs not working the way they are supposed to. There are many types of amyloidosis. Amvuttra (vutrisiran) is used to treat two kinds of amyloidosis. The first is known as hereditary transthyretin-mediated amyloidosis (hATTR) with polyneuropathy and the second is known as transthyretin amyloid cardiomyopathy (ATTR-CM).
Amvuttra is an injection that is given by a health care provider every three months under the skin to treat both hATTR and ATTR-CM.
What Is ATTR-CM?
ATTR-CM is a rare condition that happens when a broken gene causes abnormally shaped proteins to clump together. These abnormally shaped proteins can build up in many places, including nerves or the heart. When the buildup happens in the heart, it causes the walls of the heart to become stiff, which is called cardiomyopathy. It can also lead to heart failure.
ATTR-CM may cause no symptoms in people, or it may cause symptoms similar to those of heart failure, including shortness of breath, swelling, confusion, increased heart rate, or abnormal heart rhythms. This may make it hard for you to walk long distances or do activities that require energy such as climbing stairs, doing chores, or other work.
You may also have symptoms not related to the heart including weakness, numbness, pain, or tingling in your arms or legs, sweating, problems with sex, dizziness or fainting, or problems with digesting food.
How Does Amvuttra Work for ATTR-CM?
TTR is a protein that 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. People with ATTR-CM have a broken gene that makes abnormally shaped TTR. The abnormal protein builds up in different areas of the body, which is known as an amyloid deposit.
Amvuttra is known as a “gene silencer.” It causes less TTR to be made in the liver, which leads to less buildup of TTR in tissues and organs, such as the heart.
How Was Amvuttra Studied for ATTR-CM?
Amvuttra was studied in 655 people with ATTR-CM. They received either Amvuttra or placebo injections (that contain no medicine) every 12 weeks for up to three years. To be in this study, people had to be between 18 and 85 years old and have heart failure. To determine if the medicine worked, the researchers looked at whether people died or had a hospitalization or urgent visit for heart failure during the 36-month study period.
Other measures used to look at the effectiveness of Amvuttra were death from any cause after 42 months as well as improvements in the following measures:
- Changes in the six-minute walk test. This test looks at how far you can walk at a normal pace in a six-minute time period.
- New York Heart Association (NYHA) classification. This is used to measure the severity of heart failure symptoms. There are four different categories that are labeled using Roman numerals I, II, III, and IV. As the Roman numeral increases, the severity of the symptoms increases. The table below provides more information on the NYHA Classification.
NYHA Class
Description
I
Symptoms do not limit physical activity. Ordinary physical activity does not cause too much fatigue, shortness of breath, or palpitations.
II
Symptoms limit physical activity slightly. You are comfortable at rest, but ordinary physical activity may cause fatigue, shortness of breath, chest pain, or palpitations.
III
There is a lot of limitation on physical activity. You are comfortable at rest, but lighter than normal activity may cause symptoms of fatigue, palpitations, shortness of breath, or chest pain.
IV
You have symptoms at rest. Any physical activity makes it worse.
- Kansas City Cardiomyopathy Questionnaire – Overall Summary (KCCQ-OS) scoring system. This is used to measure quality of life. It uses 23 questions to measure how heart failure affects people’s lives. The questions in this scoring system ask about a person’s symptoms, including how often and how severe the symptoms are and how well they understand and can manage their heart failure. It also asks about how symptoms affect physical abilities, social interactions, and quality of life. Scores on this questionnaire range from zero to 100 and are usually grouped into categories:
- Scores of zero to 24 mean very poor to poor health status.
- Scores of 25 to 49 mean poor to fair health status.
- Scores of 50 to 74 mean fair to good health status.
- Scores of 75 to 100 mean good to excellent health status.
Who Was Included in the Study?
A total of 326 people received Amvuttra and 328 received a placebo injection. People were allowed to use another medicine for ATTR-CM called tafamidis during the study. People were told to take normal supplement doses of vitamin A during the study since Amvuttra may lower vitamin A levels in the blood.
People in this study were about 77 years old. About 93% were men. About 85% of the people in this study were White, 7% were Black, and 6% were Asian. About 88% of the people in this study had wild-type ATTR, which means they did not inherit it.
What Did the Study Find?
Death or hospitalization/urgent visit for heart failure
At the end of the three-year treatment period, the researchers analyzed the results. They separated them based on whether patients were taking tafamidis or not taking tafamidis during the trial.
- People who received Amvuttra (including those who were taking tafamidis) were 28% less likely to die or have a hospitalization or urgent visit for heart failure compared to people who received the placebo injection.
- People who received Amvuttra and who were not taking tafamidis were 33% less likely to die or have a hospitalization or urgent visit for heart failure compared to those who received the placebo injection.
Other outcomes
When the researchers looked at death from any cause at 42 months, they found that people who received Amvuttra were about 35% less likely to die at 42 months compared to those who got the placebo injections.
People taking Amvuttra also had less decline in the six-minute walk test and KCCQ-OS quality of life score compared to those taking the placebo injections. More people in the Amvuttra group also had an improvement or no change in their NYHA classification at 30 months.
Your results may differ from what was seen in clinical studies. You and your health care provider should determine if the benefits of taking Amvuttra outweigh any potential risks.
How Long Until I See the Full Effects of Amvuttra?
Amvuttra works slowly over time, so you may not see results right away. It may take a few months or longer to start seeing improvements in your symptoms.
How Do I Manage Side Effects?
Amvuttra may cause you to have low levels of vitamin A. Your health care provider may check your blood to measure your vitamin A levels. Keep all appointments for blood work while on Amvuttra. Eat a normal, healthy diet with recommended amounts of vitamin A. Foods high in vitamin A include red peppers, spinach, beef liver, sweet potatoes, ice cream, pumpkin pie, and carrots. Call your health care provider if you notice any changes in vision. Your health care provider may advise you to start taking vitamin A supplements depending on your vitamin A levels.
These are not all of the possible side effects of Amvuttra. Talk with your health care provider if you have other symptoms that are bothering you.
Is There Any Cost Assistance Available for Amvuttra?
There may be cost assistance to help you afford Amvuttra. You may have options even if you do not have health insurance. Alynlam Assist is a support program offered by the drugmaker that can help see if you are eligible for copay support, patient assistance programs, and a quick start program. You can access Alynlam Assist at www.alnylamassist.com/amvuttra/financial-assistance or by calling 833-256-2748.
