Attruby may reduce outpatient heart failure worsening in ATTR-CM
Differences versus placebo seen within 30 days, sustained to 30 months
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New analyses suggest Attruby (acoramidis) may reduce the risk of outpatient worsening heart failure, with differences seen within 30 days and sustained through 30 months in adults with transthyretin amyloid cardiomyopathy (ATTR-CM).
The analyses were based on data from the large Phase 3 ATTRibute-CM (NCT03860935) trial. In a company press release, Bridgebio, the therapy’s developer, said the findings suggest Attruby exhibits “the fastest time to impact of any disease modifying treatment in ATTR-CM.”
New analyses presented at Heart Failure 2026
These findings, along with additional ATTRibute-CM analyses and an indirect comparison of Attruby and Vyndamax (tafamidis) — another approved ATTR-CM therapy with a similar mechanism of action — were presented at Heart Failure 2026, held May 9-12 in Barcelona and virtually.
ATTR-CM is a heart disease in which the transthyretin (TTR) protein forms abnormal clumps in heart tissue, causing heart damage.
Attruby, sold as Beyonttra in the European Union, is an approved TTR stabilizer for adults with ATTR-CM. TTR stabilizers are designed to bind to TTR and help prevent it from forming disease-driving clumps.
The therapy’s approvals were based on data from ATTRibute-CM, which compared Attruby against a placebo for 30 months (2.5 years) in more than 600 adults with hereditary or non-hereditary, or wild-type, forms of ATTR-CM.
Results showed the therapy significantly decreased the risk of cardiovascular death and heart-related hospitalizations relative to the placebo.
Newly presented data showed that Attruby-treated patients had a 41% lower risk of outpatient worsening heart failure compared with those on placebo. Group differences were seen within 30 days and were sustained through 30 months.
Outpatient worsening heart failure was found to be a strong predictor of death and hospitalization due to cardiovascular disease, “reinforcing its role as an early and clinically meaningful marker of disease progression,” the release stated.
Even after adjusting for outpatient worsening heart failure, statistical analyses showed that Attruby was associated with a significantly lower risk of death and recurrent cardiovascular hospitalizations, by 41%.
TTR stabilization markers linked to survival
Other new analyses showed that Attruby was associated not only with an early and sustained increase in blood TTR levels — a marker of TTR stabilization — but also with a significant reduction in blood TTR level variability within each patient over time relative to placebo (9.5% vs. 12.8%).
Both higher blood TTR levels and lower TTR level variability were independently linked to a lower risk of death from any cause, by 54% and 44%, respectively. In statistical analyses, reduced TTR variability accounted for roughly 20% of the therapy’s effect on death risk.
“While increasing TTR levels on stabilizer therapy is important and strongly relates to risk of dying in ATTR-CM, these new results demonstrate that reducing TTR variability at the individual level over time also seems to be important for modifying disease outcomes,” said Senthil Selvaraj, MD, of the Duke University School of Medicine, who presented the data at the meeting. “By linking TTR variability independently to mortality, we’re seeing a mechanistic signal that may help explain [Attruby’s] clinical benefit, providing complementary data to support its use in ATTR-CM.”
Other ATTRibute-CM analyses shared at the conference showed that Attruby blunted the rise in NT-proBNP, a marker of heart strain, by about 50% through 30 months across relevant patient subgroups.
The therapy also slowed the decline in heart failure-related health status, with patients given Attruby being more likely than those on placebo to report stable or even improved health status over the course of the trial.
Indirect analysis compared Attruby and Vyndamax
At the meeting, researchers also presented results from an indirect comparison analysis between efficacy data from ATTRibute-CM and ATTR-ACT (NCT01994889), the Phase 3 trial that supported Vyndamax’s approvals for ATTR-CM.
Marketed by Pfizer, Vyndamax is another approved TTR stabilizer for ATTR-CM. In the European Union, the drug is sold under the brand name Vyndaqel. ATTR-ACT data showed that Vyndamax outperformed a placebo at reducing the risk of death and heart-related hospitalizations after 2.5 years.
The indirect comparison analysis, which attempted to adjust for population differences between trials by matching patients with similar characteristics at the start of each study, suggested that Attruby was associated with a significantly lower risk of cardiovascular hospitalizations, by about 34%, relative to Vyndamax.
Attruby was also associated with a 28% lower rate of death from any cause compared with Vyndamax, but this difference did not reach statistical significance, meaning it could have been due to chance. The safety profile of both medications was comparable, according to Bridgebio.
Still, this type of indirect comparison needs to be interpreted with some caution, because differences in trial design and study population may influence the results.
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