MUSC plays key role testing new treatment for ATTR-CM, serious condition affecting heart

Researchers at the Medical University of South Carolina played an important role in testing a new treatment for a condition that can lead to serious heart trouble. The condition is called transthyretin amyloid cardiomyopathy, or ATTR-CM. It’s a disease in the heart muscle that can be deadly. The new treatment is called acoramidis, brand name Attruby.

Daniel Judge, M.D., a cardiologist with the MUSC Health Heart and Vascular Center and a professor in MUSC’s College of Medicine, led the U.S. sites involved in the final phase of research that led to approval from the Food and Drug Administration. He described the problem that the drug targets.

“Transthyretin is a protein that circulates in the blood and sometimes misfolds and deposits in the heart. When that happens, it causes the heart to be very stiff, leading to congestive heart failure.” That misfolding is called amyloidosis, a term some people associate with the amyloid plaques of Alzheimer’s disease. But Judge said ATTR-CM, which involves a protein produced in the liver, is unrelated to Alzheimer’s.

In people with ATTR-CM, acoramidis can help stabilize the liver-made protein, Judge said. “It mimics something that naturally occurs and seems to be very effective.”

 

So effective that something remarkable happened during his research on the treatment. “For me, the exciting part is two things. One is my personal experience seeing it let at least one person not only stabilize - but get better.” That’s happened in a few cases in a London study site for the treatment as well, Judge said.

The other exciting part for the cardiologist is that it stabilized many other people who got the treatment. “People declined much more slowly than they did with placebo. People lived longer compared to those who got placebo. And they had less chance of hospitalization and improved quality of life compared with the placebo.”

Quality of life is important, Judge said. ATTR-CM typically affects older people. But it’s more common in some groups than others. “Many of the patients who have a genetic tendency for the condition, here in the Southeast in particular, are African American. Three-and-a-half percent have a gene variant that predisposes them to this condition.”

Hereditary ATTR-CM also affects some people of Irish ancestry and people in parts of Portugal, Brazil, Sweden and Japan, according to the American Heart Association. There’s also “wild-type” ATTR-CM, where there’s no variant in the transthyretin gene but people suffer from the condition anyway. 

Risk factors for ATTR-CM include having a relative with ATTR-CM or heart failure, being older and being male. But many times, those risk factors and/or early warning signs go unheeded. “It’s been poorly recognized. Traditionally, it’s been something that physicians often stumble over, don’t recognize,” Judge said.

“Having carpal tunnel syndrome in both hands is sometimes a sign of this condition. It’s not diagnostic, it’s not specific, but it’s one thing for doctors to think about. Like, could this be amyloid?” Judge said.

“We call them the red-flag warning signs of ATTR-CM. And mostly because it’s things that you would think are unrelated to a heart condition. How does bilateral carpal tunnel syndrome affect your heart? How does ruptured bicep tendon affect your heart? How does spinal stenosis affect your heart? It’s all because they’re interrelated by this misfolding of the protein.”

Judge got involved with research on the new treatment back in 2016. “I started to collaborate with an investigator at Stanford named Dr. Isabella Graef. And she developed this compound that we hoped would work for this disease and stabilize TTR.” 

The company BridgeBio Pharma got involved. And clinical trials soon followed. The phase 1 trial looked at whether the treatment is safe. The answer was “yes,” Judge said. Then, MUSC was the first site to do patient treatment in the phase two clinical trials, which focused on whether acoramidis works. 

More recently, phase three trials involving more than 600 people found it led to better outcomes when it came to preventing sickness and death and allowing people who got the treatment to function better in their lives. 

Judge said he served as a paid consultant to BioBridge when it came to designing the clinical trials and MUSC received support for its role in the research. But the work isn’t over, Judge said. 

“We will soon be enrolling people to try to prevent amyloid for people who carry the genetic tendency. The trial is called ACT-EARLY. The idea will be for people who carry the genetic tendency, who are close to the age where the condition happens in their family to start on treatment or placebo to see if we can, with this same therapy, not only treat ATTR-CM, but prevent it.”