Attruby slows disease progression across ATTR-CM subgroups: Trial data
Benefits detected as early as 3 months, sustained up to 3.5 years
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Attruby (acoramidis) slows disease progression and significantly reduces death and cardiovascular-related hospitalizations in adults with hereditary or wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) across several subgroups, according to new analyses of data from a clinical trial and its extension.
Benefits were detected as early as three months and were sustained for up to 3.5 years, without new safety concerns.
The new analyses of data are from the completed Phase 3 ATTRibute-CM clinical trial (NCT03860935), which supported Attruby’s approvals for ATTR-CM, and its ongoing open-label extension study (NCT04988386).
The findings were described in the study “Acoramidis in transthyretin amyloid cardiomyopathy: expanding evidence from ATTRibute-CM,” which was published in Future Cardiology by an international team of researchers. It was funded by BridgeBio, which developed and markets Attruby in the U.S. In Europe, the medication is marketed by Bayer under the brand name Beyonttra.
Attruby binds to TTR protein to help stabilize it
ATTR-CM occurs when a protein called transthyretin (TTR) breaks down, misfolds, and forms toxic clumps called amyloid fibrils. These amyloid fibrils accumulate in the heart muscle, leading to thickening and stiffening of the heart walls, thereby reducing its ability to pump blood.
The disease can be hereditary, caused by mutations in the TTR gene, or wild type, which develops sporadically with age, most often in older adults.
“ATTR-CM is associated with poor prognosis, with mortality typically occurring within 3-4 years of diagnosis due to progressive heart failure if left untreated, highlighting the need for effective, disease-modifying therapeutic interventions,” the researchers wrote.
Attruby belongs to a class of medications known as TTR stabilizers, which bind directly to the TTR protein and help stabilize it, preventing it from breaking apart. This reduces the formation of amyloid deposits, easing symptoms and slowing the progression of the disease.
Available as oral tablets, Attruby is approved in the U.S., Europe, and other regions for the treatment of adults with hereditary or wild-type ATTR-CM. Approvals were based on data from the global ATTRibute-CM study, in which 632 adults with hereditary or wild-type ATTR-CM were randomly assigned to receive either Attruby (800 mg) or a placebo, twice daily for 30 months (about 2.5 years).
The main goal was to compare Attruby with the placebo using a ranked, step-by-step analysis. The researchers looked at four outcomes in order: death from any cause, rate of cardiovascular-related hospitalizations, changes in blood levels of NT-proBNP (a marker of heart stress), and changes in six-minute walk distance (6MWD; a test of physical function and exercise capacity).
Participants completing ATTRibute-CM could enter its open-label extension study, in which all participants receive Attruby for up to five years.
Therapy associated with 23% lower risk of death from any cause
In this study, an international team of researchers reviewed data from the ATTRibute-CM study and its ongoing extension.
As previously announced, Attruby performed significantly better than the placebo at 30 months in the four-step main analysis.
New analyses showed that the therapy was associated with a 23% lower risk of death from any cause and a 50% lower risk of cardiovascular-related hospitalizations. Attruby-treated patients were also more likely to experience reductions in NT-proBNP levels (45% vs. 9%) and walked an average of 39.6 meters farther during the 6MWD test than those on a placebo.
The therapy was also associated with better quality of life, as assessed with several validated measures.
Additional analyses also demonstrated that benefits in mortality and cardiovascular-related hospitalizations were observed as early as three months and sustained through month 30.
“The magnitude of reduction in cumulative burden of cardiovascular outcomes with [Attruby] versus placebo increased progressively over time, corresponding at Month 30 to 53 events avoided per 100 patients treated with [Attruby],” the researchers wrote.
Attruby’s benefits were consistent across participant subgroups defined by ATTR-CM subtype (hereditary vs. wild-type), age at enrollment (younger than 78 vs. 78 years and older), and NT-proBNP levels at the study’s start (up to 3,000 picograms/mL vs. higher than 3,000 picograms/mL).
This comprehensive analysis of data from the ATTRibute-CM study program shows that [Attruby] provides clinical benefits across multiple [measures] and analytical approaches. Benefits began in [three] months and lasted through 42 months with no new safety concerns.
Further analyses showed that the therapy’s efficacy was maintained regardless of the NT-proBNP threshold used (at least 500, 750, or 1,000 picograms/mL) and the presence of stage 4 chronic kidney disease — a group of high-risk patients with severe kidney function loss who are typically excluded from trials.
The simultaneous use of Vyndamax (tafamidis), another TTR stabilizer approved for ATTR-CM in the U.S., did not affect the observed benefits of Attruby.
Long-term follow-up in the open-label extension study lasted up to 42 months (about 3.5 years).
Data demonstrated that Attruby’s benefits continued over time, with early treatment initiation being linked to a 33.9% reduction in the risk of death or first cardiovascular-related hospitalizations relative to delayed initiation among patients initially assigned the placebo. Continuous Attruby treatment continued to lessen the increase in NT-proBNP levels and the decline in physical function and quality of life.
No new safety problems were identified with longer treatment.
“This comprehensive analysis of data from the ATTRibute-CM study program shows that [Attruby] provides clinical benefits across multiple [measures] and analytical approaches,” the researchers wrote. “Benefits started in [three] months and lasted through 42 months with no new safety concerns.”
An ongoing Phase 3 trial, called ACT-EARLY (NCT06563895), is testing whether Attruby can prevent or delay disease onset in people who carry mutations in the TTR gene but do not yet have symptoms.
