New data suggest ATTR-CM therapy may help reverse heart damage
Trial imaging found improved heart function in some patients through 42 months
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The approved therapy Attruby (acoramidis) may not only slow the progression of transthyretin amyloid cardiomyopathy (ATTR-CM), but it may also help reverse heart damage, according to newly analyzed imaging data from a clinical trial.
Bridgebio, the company that markets Attruby in the U.S., presented these and other findings from the Phase 3 ATTRibute-CM trial (NCT03860935) and its ongoing open-label extension (OLE) study (NCT04988386) at the European Society of Cardiology (ESC) Congress 2026.
New findings raise possibility of reversing heart damage
“The clinical community is excited about the potential to restore heart health found in these data,” Marianna Fontana, MD, of University College London, said in a press release from Bridgebio. “For patients and clinicians navigating ATTR-CM, this is an exciting signal that the treatment paradigm is shifting toward a therapy that could actively restore heart health rather than only manage decline.”
ATTR-CM is a disorder in which toxic clumps of the protein transthyretin (TTR) cause damage to heart tissue. As the damage accumulates, the heart can gradually lose its ability to work properly, often leading to heart failure.
Attruby is an oral therapy that works to stabilize the TTR protein, which helps prevent it from forming toxic clumps. It is approved in the U.S. for adults with ATTR-CM to reduce cardiovascular death and cardiovascular-related hospitalization. It is similarly approved in the European Union, where it is sold under the name Beyonttra by Bayer.
The therapy’s approvals were based largely on data from the 2.5-year ATTRibute-CM study, which showed that Attruby performed better than a placebo on a four-step measure that included death from any cause, cardiovascular-related hospitalization, a marker of heart strain, and walking ability.
These data suggest that Attruby can help slow the progression of ATTR-CM. But could it also reverse heart damage that has already occurred?
Imaging analyses assess changes in heart structure and function
To find out, researchers analyzed data from an imaging substudy conducted as part of ATTRibute-CM and its OLE study, in which all participants receive Attruby and are followed for longer-term outcomes.
Previous results indicated that measures of heart structure and function generally trended toward improvement or remained stable after 2.5 years in those treated with Attruby in ATTRibute-CM, while the same measures tended to worsen or remain unchanged in those given the placebo.
Newly announced data focused on left ventricular (LV) systolic function, a measure of how well the heart’s main pumping chamber pumps blood to the rest of the body.
In a completer analysis, meaning an analysis of patients who completed the relevant assessments, LV systolic function improved after 2.5 years in more than half (54%) of Attruby-treated patients, versus 20% of those given the placebo. For comparison, 26% of patients in an independent natural history cohort showed such improvement after two years.
A more conservative analysis also favored Attruby, with improved LV systolic function in 34% of treated patients versus 9% of those given placebo after 2.5 years; 30% of patients on continuous Attruby showed improvement after 3.5 years.
“These new [imaging] data from ATTRibute-CM shows evidence of reversal in a meaningful proportion of individuals treated with [Attruby], with roughly half showing improved left ventricular systolic function in the completer analysis, more than [two times] the proportion observed in the natural history [data] from a [National Amyloidosis Centre] cohort or in ATTRibute-CM participants treated with placebo,” Fontana said.
In the completer analysis, among patients who received continuous Attruby for 3.5 years in ATTRibute-CM and its OLE study, more than half (53%) showed improvement in LV systolic function. Nearly half (46%) also showed improvement in LV mass index, a measure of the mass of the heart’s main pumping chamber relative to body size, “providing evidence of favorable structural remodeling,” the release stated.
These observations led Bridgebio to launch ASCEND-ATTR (NCT07695701), which the company describes as a Phase 3b/4 trial, to track Attruby’s effects on heart structure and function in adults with ATTR-CM over three years. The study is currently enrolling participants at a site in St. Louis, Missouri.
Attruby linked to more time alive and out of the hospital
In a separate presentation at the ESC Congress, researchers shared new ATTRibute-CM findings on days lost because of death or cardiovascular-related hospitalization (DLDCVH).
Data showed that the estimated mean percentage of DLDCVH over 2.5 years was lower in the Attruby group than in the placebo group (7.5% vs. 11.7%). That translated to 38 additional days — more than a month — alive and out of the hospital for patients treated with Attruby.
Results from the ongoing OLE study showed that the difference increased over time, reaching an observed 65 additional days alive and out of the hospital over three years compared with patients originally assigned the placebo.
ATTR-CM can be caused by mutations in the gene encoding the TTR protein. The most common ATTR-CM genetic variant globally is p.Val142Ile, which disproportionately affects people of Western African ancestry.
In another presentation, researchers focused on outcomes from 35 patients with p.Val142Ile who continued into the OLE study after ATTRibute-CM. In line with results from the study’s whole population, 4.5-year data showed that p.Val142Ile carriers who started Attruby earlier and received continuous treatment had lower all-cause mortality than those who started on placebo and switched to Attruby in the OLE study (30.4% vs. 66.7%).
Notably, both all-cause and cardiovascular mortality rates after 4.5 years were about 65% in p.Val142Ile carriers originally assigned to the placebo in ATTRibute-CM, “underscoring the substantial unmet medical need in this high-risk subgroup,” the release stated.
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