The Future of ATTR-CM Treatment

Treatments have evolved for transthyretin amyloid cardiomyopathy (ATTR-CM), which occurs when a protein called transthyretin changes shape and builds up in the heart. Instead of simply addressing symptoms, newer and future treatments target the underlying cause of ATTR-CM and can slow the disease.

“There’s a lot of excitement in this area,” says Robert DiDomenico, PharmD, an associate professor of pharmacy at the University of Illinois Chicago, where he studies treatments for heart diseases like ATTR-CM. “Before 2019, there weren’t really any therapies for ATTR-CM, other than to make people comfortable.” Now there are three medications approved by the U.S. Food and Drug Administration (FDA), with several more being investigated.

• tafamidis (Vyndamax) Tafamidis is a daily oral medication that stabilizes transthyretin proteins, making it harder for them to change shape and build up in the heart. It was the first medication approved to treat ATTR-CM. In clinical trials, it reduced deaths in people with ATTR-CM by 31 percent compared with a placebo.

  [2]

• acoramidis (Attruby) Another oral stabilizing agent, acoramidis works similarly to tafamidis but is designed to bind more tightly to the protein, which may lead to stronger stabilization, reducing the risks of hospitalization and death by about 36 percent.

  [3]

  [4]

• vutrisiran (Amvuttra) The newest ATTR-CM treatment is the first silencer agent. Vutrisiran, which is given as an injection every three months, limits the amount of transthyretin produced in the liver.

  [5]

   In clinical trials, the drug reduced the risk of death by about 36 percent and lowered the risk of cardiovascular events.

  [6]

Researchers are designing a new wave of silencing medications to treat ATTR-CM. Like vutrisiran, these gene silencers limit the production of the transthyretin protein so less of it reaches the heart.

“The net result is that the proteins never get to the point of misfolding and depositing into the heart,” Dr. DiDomenico says.

These experimental medications include the following:

• eplontersen This is a monthly injectable that's administered at home. Although it works similarly to vutrisiran, it is designed to target the liver more effectively. The FDA has already approved eplontersen to treat other types of amyloidosis, such as polyneuropathy of hereditary transthyretin-mediated amyloidosis. Phase 3 clinical trials for its use with ATTR-CM are scheduled to finish in August 2026.

  [1]

  [7]

• nucresiran Injected doses of this silencer are designed to last six months or longer. In early clinical trials, it has reduced the amount of transthyretin in blood by more than 90 percent.

  [8]

   “That’s compared with about 80 percent for other silencers,” says Kevin Alexander, MD, a cardiologist and assistant professor of cardiovascular medicine at Stanford University School of Medicine in California. FDA approval would come after a final clinical trial, the results of which may be at least a year away.

  [9]

“They bind to amyloids and promote the immune system to eat them up and remove them,” Dr. Alexander says.

“The hope is that they could be helpful for patients with later-stage disease,” who already have significant transthyretin buildup, Alexander says.

“It’s essentially a single dose that you’re giving to train the body to shut down the production of that protein for the rest of the patient’s life,” DiDomenico says.

“The initial results have been pretty encouraging,” DiDomenico says.

Larger phase 3 trials are underway and are expected to wrap up by 2028.

“Patients are certainly paying thousands of dollars, which is pretty significant, considering that this is a lifelong therapy,” DiDomenico says.

“I don’t view these things as alternatives,” he says. “They have been looked at in small studies, but those aren’t the same kind of large, randomized, controlled trials that we have for FDA-approved drugs.”

Share your financial concerns with members of your cardiology team. They can guide you toward resources for navigating your insurance coverage or accessing patient assistant or discount programs.

• Although there is no cure for ATTR-CM, the FDA has approved three medications to treat the condition, and even more impactful treatments are in the pipeline.
• The newest treatments can stabilize dysfunctional transthyretin protein, or significantly reduce its production.
• Experimental treatments being studied right now may be able to remove the dangerous proteins after they’ve formed or even stop their production entirely.