Novel drug for fatal type of heart failure proves safe and effective in phase 3 trial

Pumping over 100,000 times a day, the heart is a critical muscle needed to deliver oxygen and nutrients to our organs to sustain healthy bodily function. Unfortunately, heart failure affects an estimated 6.2 million people in the U.S. and a staggering 64 million worldwide.

Of older patients with heart failure and abnormally thickened hearts, as many as one in five have an underdiagnosed, highly progressive and fatal condition called transthyretin amyloid cardiomyopathy, or ATTR-CM. The disease, which can be hereditary or develop spontaneously, is defined by an accumulation of misfolded transthyretin (TTR) proteins in the heart. These protein deposits weaken the heart muscle and, over time, cause extreme restriction of heart function, leading to failure.

Patients with the most common form of ATTR-CM frequently face misdiagnosis in clinics due to limited disease knowledge and symptoms that resemble other more common heart-related conditions. Additionally, they contend with a scarcity of approved drugs, as the sole available treatment specifically indicated for the most common form of ATTR-CM costs about $225,000 per year and is not readily accessible.

Investigators for the ATTRibute-CM phase 3 trial report in the New England Journal of Medicine that the novel drug acoramidis showed promise against ATTR-CM and is safe. Their data show that acoramidis achieves near-complete stabilization of the TTR proteins, which may slow or halt disease progression. Based on the efficacy and safety data from this randomized, multicenter, controlled 30-month study, BridgeBio Pharma (Palo Alto, CA) is seeking approval from the Food and Drug Administration (FDA) for use in these patients.  

“We hope that, when this drug receives approval from the FDA, it will create competition in the market and drive down the cost of these incredibly expensive medications,” said Daniel Judge, M.D., a cardiologist at the Medical University of South Carolina who is also an ATTRibute-CM investigator and co-leader of the trial’s steering committee.

Judge and his colleague, Isabella Graef, M.D., of Stanford University have dedicated years to researching and developing a novel treatment for these patients. Graef spearheaded the creation of the new drug targeting misfolded proteins central to the disease, and Judge has since been heavily involved in phase 2 and 3 clinical trials, testing the new drug in his clinic at MUSC. In fact, MUSC was one of the first sites in the world to enroll patients into the ATTRibute-CM phase 3 trial.

The ATTRibute-CM investigators found that acoramidis binds to circulating TTR protein, preventing it from depositing as amyloid. Compared with placebo, acoramidis reduced hospitalizations for heart-related events, decreased cardiac congestion as determined by blood tests and increased the distance walked over six minutes.

In data shown by Judge at the American Heart Association, the number of people needed to treat with acoramidis to prevent one cardiovascular hospitalization in one year during this study was five. Overall, treatment adverse events were low and similar in both the acoramidis and placebo groups, indicating that the drug is safe. These data hold great promise for ATTR-CM patients and suggest that acoramidis may halt disease progression and increase survival rates.

With over 20 years of practicing cardiology and specializing in translational research targeting heart disease, Judge has recruited and followed several patients involved with the acoramidis clinical trials. He and his co-investigators have witnessed the novel drug move through translational testing and have been able to see the direct benefit to real patients suffering with ATTR-CM.

“Early in my career, I was disappointed by the lack of any available treatments. I’m glad to see another successful trial for ATTR-CM,” said Judge. “A patient whom I first met in 2017 had a prognosis of three years. Fast forward to 6.5 years later, and this same patient, who was one of the first participants enrolled at MUSC in the phase 2 trial, seems to be getting better due to acoramidis.”

If the disease can be stabilized, the hope is that the heart can improve gradually. Safely and effectively halting disease progression with acoramidis could provide improved quantity and quality of life for patients worldwide suffering from ATTR-CM.

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About MUSC

Founded in 1824 in Charleston, MUSC is the state’s only comprehensive academic health system, with a unique mission to preserve and optimize human life in South Carolina through education, research and patient care. Each year, MUSC educates more than 3,200 students in six colleges – Dental Medicine, Graduate Studies, Health Professions, Medicine, Nursing and Pharmacy – and trains more than 900 residents and fellows in its health system. MUSC brought in more than $298 million in research funds in fiscal year 2022, leading the state overall in research funding. MUSC also leads the state in federal and National Institutes of Health funding, with more than $220 million. For information on academic programs, visit musc.edu.

As the health care system of the Medical University of South Carolina, MUSC Health is dedicated to delivering the highest-quality and safest patient care while educating and training generations of outstanding health care providers and leaders to serve the people of South Carolina and beyond. Patient care is provided at 16 hospitals (includes owned and equity stake), with approximately 2,700 beds and four additional hospital locations in development; more than 350 telehealth sites and connectivity to patients’ homes; and nearly 750 care locations situated in all regions of South Carolina. In 2022, for the eighth consecutive year, U.S. News & World Report named MUSC Health University Medical Center in Charleston the No. 1 hospital in South Carolina. To learn more about clinical patient services, visit muschealth.org.

MUSC has a total enterprise annual operating budget of $5.1 billion. The nearly 26,000 MUSC family members include world-class faculty, physicians, specialty providers, scientists, students, affiliates and care team members who deliver groundbreaking education, research, and patient care.