The heart is a vital muscle that beats over 100,000 times a day, delivering oxygen and nutrients to organs to maintain healthy bodily function. Unfortunately, heart failure affects an estimated 6.2 million people in the United States and a staggering 64 million people worldwide.
Among older patients with heart failure or abnormally thickened hearts, one in five suffer from the late-diagnosed, progressive and fatal transthyretin amyloid cardiomyopathy (ATTR-CM). The disease, which can be inherited or occurring naturally, is caused by the accumulation of abnormally folded transthyretin (TTR) protein in the heart. These protein deposits weaken the heart muscle and, over time, severely limit cardiac function, leading to heart failure.
Patients with the most common form of ATTR-CM are often misdiagnosed in the clinic due to limited knowledge about the disease and symptoms that mimic other common heart-related diseases. Additionally, they also suffer from a shortage of approved medications, as the only treatment specifically indicated for the most common form of ATTR-CM costs approximately $225,000 per year and is not readily available.
“Early in my career, I was frustrated by the lack of a cure. [for ATTR-CM]”The first patient seen in 2017 had a three-year prognosis. Six and a half years later, this same patient, one of the first participants in MUSC’s Phase 2 trial, appears to be on the mend with Acoramidis.” –Daniel Judge, MD
Investigators from the ATTRibute-CM Phase 3 trial report in the New England Journal of Medicine that the novel drug Acoramidis is promising and safe for ATTR-CM. Their data suggest that Acoramidis almost completely stabilizes the TTR protein, potentially slowing or halting disease progression. Based on 30-month efficacy and safety data from this randomized, multicenter, controlled trial, BridgeBio (Palo Alto, CA) is seeking U.S. Food and Drug Administration (FDA) approval for use in these patients.
“We hope that FDA approval of this drug will bring competition to the market and bring down the cost of this very expensive drug,” said Daniel Judge, MD, a cardiologist at the Medical University of South Carolina, an investigator in ATTRibute-CM and co-leader of the trial’s steering committee.
Judge and his Stanford colleague, Isabella Graef, MD, PhD, have spent years researching and developing new treatments for these patients. Graef led the development of new drugs that target the misfolded proteins at the heart of the disease, and Judge has since been deeply involved in Phase 2 and 3 clinical trials, testing the new drugs in the MUSC clinic. In fact, MUSC was one of the first centers in the world to enroll patients in the ATTRibute-CM Phase 3 trial.
ATTRibute-CM researchers found that Acoramidis binds to the circulating TTR protein and prevents it from being deposited as amyloid. Compared to placebo, Acoramidis reduced hospitalizations for heart-related events, reduced cardiac congestion as measured by blood tests, and increased six-minute walk distance.
According to data Judge presented at the American Heart Association, during the study period, the number of people who needed to be treated with Acoramidis to prevent one cardiovascular hospitalization per year was five. Overall, adverse events from treatment were low and similar in both the Acoramidis and placebo groups, indicating the drug is safe. These data offer great hope for patients with ATTR-CM, suggesting that Acoramidis has the potential to halt the progression of the disease and increase survival rates.
Judge, who has practiced cardiology for over 20 years and specializes in translational research in cardiac disease, has recruited and followed several patients in clinical trials of Acoramidis. Judge and his collaborators have watched the drug progress through translational testing and have seen it provide direct benefit to real patients suffering from ATTR-CM.
“Earlier in my career, I was frustrated by the lack of a cure, so I am pleased with the success of the new ATTR-CM trial,” said Judge. “The first patient I saw in 2017 had a three-year prognosis. Six and a half years later, this same patient, one of the first participants in MUSC’s Phase 2 trial, appears to be on the mend thanks to Acoramidis.”
“If we can stabilise the disease, it is expected that the condition of the heart will gradually improve. If we can safely and effectively halt the disease progression with Acoramidis, it has the potential to improve the quality and quantity of life for patients suffering from ATTR-CM around the world.”
reference
Gillmore JD, Judge DP, Cappelli F, et al; ATTRibute-CM Investigators. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. N Engl J Med. 2024 Jan 11;390(2):132-142. doi: 10.1056/NEJMoa2305434. PMID: 38197816.
