What to know about ATTR-CM and treatment options

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a type of heart failure. It is a rare disease that leads to a buildup of the transthyretin (TTR) in the left ventricle, the heart’s main pumping chamber. Transthyretin is a protein that helps transport thyroxine, which regulates the metabolism and retinol in the body, but when it accumulates in the left ventricle it thickens and stiffens the heart muscle. That thickening causes shortness of breath and heart failure. Other symptoms include swelling in the lower legs, chest congestion, increased heart rate and heart palpitations.

Hereditary ATTR-CM is more common in Black individuals, and it is often caused by the Val122Ile mutation. Other risk factors for the hereditary disease include being older, having a family member who has ATTR-CM and being male. If immediate family members have the disease, doctors recommend genetic testing

It is estimated that in the United States approximately 120,000 people have ATTR-CM. But the incidence and prevalence of ATTR-CM are increasing. In one study in France, incidence rates of ATTR-CM increased from 0.6 per 100,000 person-years in 2011 to 3.6 per 100,000 person-years in 2019.

Another study estimated trends in the United States and was published in January 2025 in the Journal of Cardiac Failure. Investigators assessed data from three U.S. claims databases: Merative MarketScan Medicare and Commercial databases for claims from 2010 to 2021 and IQVIA PharMetrics Plus for claims from 2016 to 2023. They found that both incidence and prevalence increased, especially for older people, and more men were diagnosed with the disease than women.

Treatment options

Since 2019, three disease-specific therapies have been approved to treat patients with ATTR-CM. The first was Pfizer’s Vyndamax (tafamidis) in May 2019, which was approved for both wild type and hereditary ATTR-CM. It has a 2025 list price of $22,332.29 for 30 capsules.

Alnylam Pharmaceuticals’ Amvuttra (vutrisiran) was initially approved 2022 to treat both wild-type and hereditary ATTR-CM. It works by “knocking down” TTR production. In March 2025, the FDA approved Amvuttra for polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Amvuttra has a wholesale acquisition cost of $119,351 per prefilled syringe.

BridgeBio Pharma’s Attruby (acoramidis) was approved in November 2024. Attruby is an oral small molecule stabilizer of transthyretin. It was designed to mimic the protective effects of the T119M mutation, which has been associated with reduced risk of vascular events. It launched with a list price of $18,759 for a month’s supply.

The Institute for Clinical and Economic Review (ICER) conducted a comparative effectiveness analysis of these therapies. ICER released a final report in October 2024. An independent appraisal committee voted that clinical evidence at the time was adequate to demonstrate superior net health benefits for all three products when compared with no disease-specific therapy.

But ICER found that the prices of two products they reviewed — Vyndamax and Attruby — were too high to achieve cost-effectiveness. Both of these products would achieve common thresholds for cost-effectiveness if priced between $13,600 and $39,000 per year. Amvuttra was not assessed because of the time and availability of the information on this product.

All three products offer a $0 copay savings card for those with commercial insurance. Patients with Medicare now have an annual out-of-pocket (OOP) cap for covered Part D medicines of $2,100 for 2026, which can be paid over the course of the entire year.

These treatment-specific therapies offer advantages in terms of reducing the risk of hospitalization and mortality, but the high costs remain a barrier for access. Treatment recommendations from UpToDate say there is possible benefit from combining therapy such as Vyndamax or Attruby plus Amvuttra, but there is not enough evidence to recommend combination treatment.

Another treatment option is the use of the nonsteroidal anti-inflammatory drug diflunisal, but UpToDate says this is rarely used because of poor tolerance and unclear efficacy.

Onpattro is approved to treat polyneuropathy of hereditary ATTR (hATTR), which can result in numbness, tingling, weakness, and pain. Onpattro, however, is not approved to treat ATTR-CM.

In the pipeline, a one-time gene therapy is in development to treat patients with ATTR-CM. Intellia Therapeutics and Regeneron are collaborating on an ongoing phase 1 trial of nexiguran ziclumeran (nex-z), which uses the CRISPR/Cas9 gene editing technology.

Nex-z is designed to inactivate the TTR gene that encodes for the transthyretin (TTR) protein. Interim data showed the administration of nex-z led to consistent, deep, and long-lasting TTR reduction. Nex-z was generally well tolerated, and the most common treatment-related adverse events were infusion-related reactions and transaminase elevations. These results were shared at the November 2025 American Heart Association (AHA) Scientific Sessions meeting.