Hereditary transthyretin amyloidosis is a rare disease in which abnormal proteins form amyloid fibrils (tiny threadlike structures) that damage your organs. It’s a chronic condition that will likely require long-term — maybe even lifelong — treatment. In recent years, doctors and researchers have developed several new hATTR amyloidosis treatments.
If you’re living with hATTR amyloidosis, your doctor may recommend that you start one of several new treatment options. Ongoing studies continue to show more about the long-term effects of these medications.
Read about life expectancy with hATTR amyloidosis.
For years, liver transplantation was the gold standard in treating hereditary ATTR amyloidosis because abnormal TTR proteins are produced in the liver. Normally, these proteins fold into specific tetramers (molecules made up of four identical molecules) that help them function properly and interact with other proteins.
In hATTR amyloidosis, TTR proteins are misfolded, changing their shape so that they clump together. These aggregations (masses) lead to organ damage and dysfunction. People with hATTR amyloidosis may develop:
Treatments for hATTR amyloidosis help address symptoms and stave off complications, either by keeping amyloid deposits from forming in organs or by preventing TTR proteins from being made.
Because TTR proteins fold improperly in hATTR amyloidosis, doctors and researchers have developed treatments that stabilize them. Tafamidis and tafamidis meglumine (Vyndaqel) are the only FDA-approved TTR stabilizers.
Diflunisal (Dolobid) is a nonsteroidal anti-inflammatory drug (NSAID) that also acts as a TTR stabilizer. It was previously studied for treating hATTR amyloidosis with cardiomyopathy but hasn’t been approved by the FDA. Instead, doctors treating this disease prescribe diflunisal off-label, which means that the drug is being used for a different purpose than what the FDA approved.
Gene-silencing therapies for treating hATTR amyloidosis are known as RNA interference (RNAi) therapeutics. Your DNA provides instructions for making thousands of different proteins. These instructions are copied and made into messenger RNA (mRNA), which then travels out to your cells’ protein-making factories. RNAi attaches to specific mRNA, preventing it from reaching these factories.
RNAi therapies that are used to treat hATTR amyloidosis recognize and block the instructions for making TTR proteins — as a result, your cells no longer make them. There are currently three approved gene-silencing therapies:
Patisiran is given as an intravenous (IV) infusion, and inotersen and vutrisiran are administered as subcutaneous (under the skin) injections. The authors of a 2022 JAMA study noted that vutrisiran offers the convenience of being administered once every three months, compared with every three weeks for patisiran.
Participants who complete a clinical trial may choose to stay in an open-label study. This is a continuing study that investigates the drug over the long term. The results of open-label studies tell researchers more about any new side effects that occur after using a drug for several years or whether effectiveness continues over time.
Tafamidis was approved by the FDA in 2019, and some studies are now showing this drug’s long-term safety and efficacy. One study published in the Journal of Protein Folding Disorders observed participants taking a placebo and/or tafamidis for up to six years. (A placebo is a substance that looks like a medical treatment but has no active ingredients. Comparing the drug versus the placebo helps researchers determine the effects of the actual treatment.)
Researchers divided the participants into two groups: One group took a placebo for 18 months and then switched to tafamidis, and another group took tafamidis for the entire study. The results showed that participants who took tafamidis during the whole study had better neurological function than those who started with the placebo. This means that tafamidis was more effective, and it delayed disease progression when taken for a longer time. Quality-of-life scores, which reflect a person’s overall well-being and ability to do daily activities, also improved in those who took tafamidis compared with those taking the placebo.
Additionally, the study found that tafamidis is generally safe — 25.8 percent of the 93 participants experienced at least one serious adverse event, such as chest pain and urinary tract infections. There were no deaths associated with treatment.
A more recent study looked at survival in people with hATTR amyloidosis and cardiac involvement. One group treated their condition with tafamidis, and the other with a placebo. Results showed that those who used tafamidis had significantly better survival rates compared with those who took a placebo.
The FDA approved patisiran in 2018 to treat polyneuropathy (damage to multiple peripheral nerves) caused by hATTR amyloidosis. Patisiran is a small interfering RNA (siRNA) drug that breaks down mRNA for the TTR gene. A handful of studies have begun to look at the long-term effects of this drug for up to five years.
One study followed people with transthyretin cardiac amyloidosis who took patisiran over two years, as well as people who started out using a placebo and switched to patisiran. Results showed that people who used patisiran the whole time continued to experience benefits from treatment over 24 months. In people who switched to patisiran, their condition often stabilized, or disease progression slowed, once they started the drug. Overall, people who took patisiran were less likely to have disease progression during the study.
The most common side effect reported during the study was infusion-related reactions.
Inotersen was approved by the FDA in 2018 after a clinical trial showed that it improved participants’ modified Neuropathy Impairment Scale + 7 (mNIS +7) scores and quality of life. Long-term studies following people from three to 6.2 years after starting treatment have found that inotersen is safe and effective. The drug continued to slow disease progression, and no unexpected side effects were reported. The most common side effects included thrombocytopenia (low platelet count), diarrhea, and nausea.
If you take inotersen, your doctor will perform blood work to regularly check your kidney function and blood cell counts. This is to monitor for any serious side effects that interfere with your kidneys’ ability to filter your blood or your blood’s ability to clot.
The FDA approved vutrisiran in June 2022 for treating neuropathy caused by hATTR amyloidosis. A phase 3 clinical trial known as Helios-A compared vutrisiran to patisiran to confirm that the medication is safe and effective. Over the course of nine months, study investigators found that vutrisiran successfully reduced the amount of TTR protein in the blood and significantly improved symptoms caused by peripheral neuropathy.
The most common side effects of vutrisiran included diarrhea, peripheral edema (swelling in the legs and feet), dizziness, and joint pain. Some people reported shortness of breath and low vitamin A levels as well. There were two reported cases of interference with the heart’s electrical rhythm.
Because of the recent approval, longer-term data is not yet available. Doctors and researchers have started another clinical trial, Helios-B, to compare vutrisiran to a placebo (in this case, a saline injection). This study is set to last seven years and will provide more information on the long-term safety and efficacy of the drug.
All medications — even those sold over the counter — come with side effects, so you’ll need to weigh the risks and benefits when beginning a new treatment. It’s important to make sure you’re likely to gain benefits that outweigh the treatment’s potential risks. Your doctor will help you better understand your risks and how they may be affected by your age, overall health, and hATTR amyloidosis symptoms.
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