Acoramidis Halves Cumulative CV Events Within 6 Months: ATTRibute-CM

MINNEAPOLIS, MN—Treatment with acoramidis (Attruby; BridgeBio Pharma) compared with placebo appears to reduce cumulative cardiovascular events by almost half among patients who have transthyretin amyloid cardiomyopathy (ATTR-CM) and clinical heart failure, with much of the benefit occurring in the early months, according to exploratory data from ATTRibute-CM.

The US Food and Drug Administration approved the oral transthyretin stabilizer in 2024 for treatment of adults with ATTR-CM on the basis of the original trial findings. Acoramidis joins tafamidis (Vyndaqel and Vyndamax; Pfizer) and, more recently, vutrisiran (Amvuttra; Alnylam) in bringing fresh treatment options for patients with this rare disease, although the agents have drawn criticism over their price tags and mortality remains high.

Still, the totality of the evidence increasingly supports the need to diagnose ATTR-CM and start treatment as quickly as possible, Ahmad Masri, MD (Oregon Health & Science University, Portland), who presented the post hoc analysis at the Heart Failure Society of America 2025 Annual Scientific Meeting, told TCTMD.

“The time-sensitive nature of transthyretin cardiomyopathy is something that has been on many people’s minds, but I think this is the first piece of evidence that should push us forward,” he said, adding that it commonly takes at least 6 months, if not 12, for patients to be diagnosed. “And then even once you establish the diagnosis, a lot of the time it ends up being that the patients have to then come back for therapy and treatment discussions, and that again adds more time.”

He urged clinicians to “condense our workup and the ability to initiate therapy early.”

Fast Results

For the modified intention-to-treat analysis, simultaneously published in JACC, Masri and colleagues included 611 patients (mean age 77.2 years; 90.8% male) from ATTRibute-CM who were randomized to acoramidis (n = 409) or placebo (n = 202). Notably, concomitant tafamidis was not allowed during the first 12 months of the trial, but 17.5% of patients in total used the drug thereafter.

By 30 months, acoramidis reduced the cumulative risk of CV mortality or recurrent CV hospitalization by a relative 49% compared with placebo (33.3% vs 48.5%; HR 0.51; 95% CI 0.43-0.62). About one-fifth of CV deaths and CV hospitalizations (19% and 22%, respectively) occurred within the first 6 months, with the curves beginning to split by about the first month. By month 30, treatment with the study drug resulted in 53 events avoided per 100 patients.

Masri said he was surprised at the extent of the benefit detected with acoramidis and how quickly it seems to work, “because our prior knowledge from other trials is that usually it does take some time for an effect to start to be observed.” Also, because one-quarter of events take place by 6 months, “it’s not true that you have to observe patients for years and years and years before you see something happen,” he added.

From here, “the open question in my mind is: are there other mechanisms of treating these TTR patients based on the different therapies that can allow this early benefit that is seen aside from only preventing further amyloid from depositing in the heart?” Masri asked.

‘Very Tangible’ Outcomes

Discussing the study after the presentation, Hanna Gaggin, MD (Massachusetts General Hospital, Boston), spoke to the importance of recording recurrent events. “I used to read studies and think of ‘happily ever after,’ but that’s not the ending that really matters. It’s what happens after that first event that also matters just as much,” she said.

Her two main takeaway messages from the analysis relate to “how remarkable the hazard ratio reduction is for acoramidis versus placebo,” especially considering no use of tafamidis for the first 12 months of the study and the early separation of the curves.

One month is a “ridiculously short period of time in which to think about how much these medications can take effect and impact our patients,” Gaggin said. “With outcomes such as cardiovascular mortality and recurrent cardiovascular hospitalization, these are very tangible, hard clinical outcomes that we have to care about.”

She said studies like this are “changing the way” she thinks about treatment for ATTR-CM, recalling how she used to wait as long as 18 months before starting medications. “Earlier diagnosis [and] earlier treatment can make a huge difference,” Gaggin agreed.