Hereditary transthyretin amyloidosis (hATTR) is a rare inherited disorder that gets worse over time. It often affects the nerves, heart, liver, and kidneys, but it can also affect other organs. Treatment of hATTR depends on your symptoms and how far the condition has progressed.
There are different stages of hATTR with nerve damage, and the number of the stage goes up from 0 to III as the condition gets worse. People with stage I have mostly mild symptoms, and walking is not affected. People with stage II have moderate impairment and need help to walk.
Onpattro (patisiran) was approved by the FDA in 2018. It was the first treatment approved in the U.S. for nerve damage (polyneuropathy) caused by hATTR. It was also the first type of “RNA interference (RNAi)” medicine approved by the FDA.
What Is Onpattro?
Onpattro is used to treat nerve damage (polyneuropathy) caused by hATTR in adults. It is given by a health care provider as an infusion into a vein (IV).
How Does Onpattro Work?
People with hereditary transthyretin amyloidosis (hATTR) have a change in a gene (mutation) that causes the liver to make abnormal forms of a protein called transthyretin (TTR). Transthyretin helps move vitamin A and thyroxine (a thyroid hormone) throughout the body.
In hATTR, the abnormal transthyretin proteins clump together and form deposits called amyloids. These amyloid deposits can build up and damage tissues, nerves, and organs, which can lead to serious problems and death.
When the deposits build up and damage the nerves (polyneuropathy), it can affect your ability to sense or feel things. This can lead to a variety of symptoms, including trouble walking, seeing, hearing, or feeling. It can also affect other important body functions, such as going to the bathroom, digestion, sweating, and blood pressure or heart rate.
Onpattro is called an RNA interference medicine based on how it works. You may also hear it called a small interfering RNA (siRNA). As these terms suggest, Onpattro interferes with and causes the breakdown of messenger RNA (mRNA) that the body needs to make transthyretin proteins. By doing this, Onpattro helps lower the amount of both normal and abnormal transthyretin proteins. This can help lower the buildup of amyloid deposits. You may also hear Onpattro called a “gene silencer” medicine because it breaks down the RNA genetic template used to make transthyretin proteins.
Onpattro is also a “lipid complex.” This means the medicine (patisiran) is in a fat (lipid) complex, or carrier. This helps the medicine better reach and get into the liver cells where it needs to work.
How Was Onpattro Studied?
A study was done to see how well Onpattro worked in adults with nerve damage caused by hereditary transthyretin amyloidosis (hATTR). People in the study were randomly assigned to get an infusion of either Onpattro or a placebo containing no medicine every three weeks for 18 months.
There were 225 people in the study; 148 of them received Onpattro and 77 received the placebo. Neither the people in the study nor their health care providers knew if they were getting Onpattro or placebo.
The main goal of the study was to see if nerve damage got worse or better. Researchers used a scoring system called the “modified Neuropathy Impairment Score +7” (mNIS+7) as a way to measure nerve damage. To find a person’s score, a health care provider uses a standard rating for factors such as muscle strength, reflexes, nerve function, and sensation. If there is a change in the scores people have from the beginning to the end of the study, this helps show how well the medicine works.
People in the study were between the ages of 24 and 83. The median age was 62, meaning that half were younger and half were older. Overall, 74% of people in the study were male. About 72% of people in the study were White, 23% were Asian, 2% were Black, and about 3% total were another race, more than one race, or race was not reported. Twenty-one percent of people were in North America, 44% were in Western Europe, and 36% were from the rest of the world.
The median (midpoint) time since people in the study had been diagnosed with hATTR was about 1.4 years. Almost everyone in the study had stage I (46%) or stage II (53%) of hATTR nerve damage. So about half needed help walking.
What Was the Main Benefit of Onpattro Seen in the Study?
At the beginning of the study, the average mNIS+7 score was 80.9 for people using Onpattro and 74.6 for people using the placebo. Higher mNIS+7 scores suggest worse nerve damage, and the maximum score is 304 points.
At 18 months, over half (56%) of people who got Onpattro had a lower mNIS+7 score, which meant that they improved. In contrast, only 4% of people who got the placebo saw improvement.
Further, among people who had a higher (worse) mNIS+7 score at month 18, the increase was less among people who got Onpattro (median of 9.9 points) as compared with those who got the placebo (median of 26.5 points).
Overall, nerve damage got worse over time in most people using placebo (no medicine), while over half of the people using Onpattro had some improvement.
Your results may differ from what was seen in clinical studies.
What Can I Expect When Starting Onpattro?
Your dose of Onpattro will be based on your weight. Onpattro is infused slowly into a vein by a health care provider. It will take about 80 minutes for you to receive each dose. Onpattro is typically given once every three weeks.
In some cases, you may be able to receive Onpattro at home from a health care provider after you get your first few doses in a clinic, infusion center, or hospital. This is a decision between you and your health care provider, and it may not be covered by insurance. Talk with your health care provider if you have any questions about this option.
If you miss an appointment to get your Onpattro dose, call your health care provider right away to reschedule. If you are able to get your dose within three days of your missed dose, you can usually continue on your original schedule. If you get your dose more than three days after your missed dose, you may need to reset your schedule and get your future doses every three weeks afterward.
It may take some time for you to start seeing any benefits of Onpattro. In the study, some people started to see a change in their mNIS+7 score after nine months of using the medicine. Keep all appointments with your health care provider to check your symptoms. Your health care provider may also do blood work or other tests to see how well Onpattro is working for you. Onpattro is usually given long-term, and you should not stop receiving Onpattro unless you have talked with your health care provider.
Your health care providers can also help you manage any other symptoms you may have from hATTR, such as heart, eye, or kidney symptoms. If you see a physical therapist, they can show you exercises that may help you walk better.
How Can I Prevent or Manage Side Effects?
Infusion reactions. Infusion reactions are common with Onpattro, and they can sometimes be severe. Your risk of an infusion reaction may be higher the first or second time you get this medicine. In one study, about 1 in 5 people treated with Onpattro had infusion reactions, compared to about 1 in 10 people who received a placebo with no medicine. In the people using Onpattro who had an infusion reaction, about 4 in 5 of them had the first infusion reaction within receiving the first two Onpattro doses, and the reactions became less frequent over time.
Everyone in the studies of Onpattro took medicines before their doses (“premedicines”) to help lower the risk of these infusion reactions. Your health care provider may recommend that you take the following medicines by mouth or as an injection into a vein (IV) to help lower your risk of an infusion reaction.
- Acetaminophen (Tylenol)
- An antihistamine (H1 receptor blocker), such as diphenhydramine
- A corticosteroid, such as dexamethasone
- An H2 receptor blocker, such as famotidine
These medicines will usually be given at least one hour before the start of each Onpattro dose. Follow your health care provider’s instructions about how to use these medicines. If you have any side effects from these medicines, tell your health care provider. They may adjust your dose.
In studies, the most common symptoms of an infusion reaction were flushing (redness or warmth of the face or skin), back pain, nausea, stomach pain, shortness of breath, and headache. Some people also had lightheadedness or fainted. Tell your health care provider right away if you have any of these symptoms while receiving your Onpattro dose or afterward. Your health care provider may adjust, pause, or stop your dose of Onpattro. They may also adjust your dose of premedicines before your next Onpattro dose to help lower your risk of infusion reactions.
Low vitamin A levels. Onpattro may cause low vitamin A levels, which could lead to vitamin A deficiency. This might be because Onpattro helps stop the formation of transthyretin, and transthyretin helps move vitamin A throughout the body. Low vitamin A levels can lead to problems with your eyes, vision, and skin.
You need to be sure you get enough vitamin A while you are using Onpattro. The amount of vitamin A you should get each day (the recommended daily amount) depends on your age and sex assigned at birth. Vitamin A is found in several foods, such as fish, liver, dairy, and some fruits and vegetables. You can also get vitamin A from vitamin A supplements. You should not take doses of vitamin A higher than the recommended daily amount. Talk with your health care provider about how much vitamin A to get through your diet and whether to take a vitamin A supplement. Too much vitamin A can cause problems, so be sure to tell your health care provider about everything that you take, such as a multivitamin.
Symptoms of low vitamin A levels may include night blindness (trouble seeing in low light) or other eye or vision changes, such as hazy vision, dry or crusty eyes, or clouding in your eye. Skin problems, such as itching, dryness, or scaling, can also happen with low vitamin A levels, and you may also have a higher risk of infections. Tell your health care provider right away if you have any of these symptoms.
How Can I Get Onpattro?
A health care provider can prescribe and order Onpattro for you, and you will likely receive it in a clinic, infusion center, or hospital.
The drugmaker has resources and financial assistance options that can help you afford Onpattro, whether or not you have insurance. Your health care provider can help you get set up with one of these programs, and a case manager can discuss your options with you. There are also health care providers that can help you better understand the medicine and how to use it. You can find more information at www.alnylamassist.com/onpattro or by calling 833-256-2748.
