Long-term therapy slows health decline for ATTR-CM patients
Attruby significantly slows drop in patient-reported health status
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Long-term therapy with Attruby (acoramidis) significantly slows the decline in heart failure-related health status — a patient-reported assessment of symptoms, physical function, and quality of life — in adults with transthyretin amyloid cardiomyopathy (ATTR-CM).
That’s according to data from the global Phase 3 ATTRibute-CM clinical trial (NCT03860935), which also showed that Attruby-treated patients were more likely than those on the placebo to score “not worse,” “well,” or “better” on a standardized measure of health status after 2.5 years of treatment.
“These results suggest meaningful patient-centered benefits and clinically relevant modification of disease trajectory with [Attruby],” the researchers wrote.
The study, “Effect of Acoramidis on Heart Failure–Related Health Status,” was published in JAMA Cardiology.
Patient input ‘essential’
ATTR-CM is caused when toxic clumps of abnormal transthyretin protein, called amyloid fibrils, accumulate in the heart muscle, gradually interfering with its ability to pump blood. The disease can be inherited through mutations in the TTR gene, which encodes transthyretin, or develop sporadically with advancing age (known as wild-type).
As the disease progresses, it can lead to worsening ATTR-CM symptoms and heart failure, which results in further physical limitations and declining quality of life.
“Patient-reported outcomes are, therefore, essential for evaluating the impact of new therapies,” the researchers wrote. They looked at how Attruby, an ATTR-CM-approved therapy, affects patients with heart failure. As a measure, they used the Kansas City Cardiomyopathy Questionnaire (KCCQ), which they said “captures the impact of HF on patients’ lives from their own perspectives.”
Attruby, marketed in the U.S. by BridgeBio Pharma, is an oral therapy approved to reduce cardiovascular-related hospitalization or death in adults with hereditary or wild-type ATTR-CM. It’s designed to stabilize transthyretin, suppress the formation of amyloid fibrils, and either slow or prevent disease progression.
The researchers analyzed data from the ATTRibute-CM study, top-line data from which had supported Attruby’s regulatory approvals for ATTR-CM. Of the 632 participants originally enrolled, 611 were included in this analysis: 409 assigned to Attruby and 202 to the placebo. Participants’ mean age was 77.2, and 9.2% were women.
Heart failure-related health status was assessed using the KCCQ-OS, scored from 0 to 100. Higher scores indicate better health.
At the study’s start, the mean KCCQ-OS scores were similar between the Attruby and placebo groups (71.7 vs. 70.5 points). Scores declined (worsened) for both groups over the course of the study, which the team noted was consistent with the disease’s progressive nature.
Still, differences between the groups emerged in the first three months and became statistically significant after month 9. By month 30 (about 2.5 years), mean KCCQ-OS scores had dropped significantly less in the Attruby group than in the placebo group (11.5 vs. 21.4 points), “corresponding to a moderate clinical benefit,” the researchers wrote.
Similar patterns were observed in additional analyses, including analyses of directly observed data and data excluding participants who also received Vyndamax (tafamidis), another approved therapy, at any time during the study.
Changes in all KCCQ-OS individual categories favored Attruby over the placebo, with the largest differences between groups observed in the domains of quality of life and self-efficacy, or a patient’s ability to cope with and manage their disease.
The researchers also looked for the number of patients who experienced clinically meaningful KCCQ-OS changes at month 30. They found that significantly more Attruby-treated patients fell into the “alive and not worse” category, defined as a KCCQ-OS decrease of less than 5 points, than those on the placebo (46.6% vs. 29.8%).
Similar results were observed for the “alive and well” category, defined as a score above 60 with less than a 10-point decrease (45.8% vs. 31.4%), and for “alive and better,” or a score increase of more than 5 points (25.3% vs. 13.8%).
Using all three measures, researchers calculated how many patients would need to be treated with Attruby for one additional patient to reach that outcome. The results showed six people must be treated for one person to reach the “alive and not worse” category, seven for “alive and well,” and nine for “alive and better.”
Attruby’s benefit on health status was similar across patient subgroups, including those grouped by TTR mutation, NT-proBNP levels (a marker of heart strain), kidney function, age, country of enrollment, and heart failure symptom class.
“These findings demonstrate that the survival and [cardiovascular-related hospitalizations] benefits of [Attruby] are accompanied by meaningful stabilization of patient-reported health status in ATTR-CM,” the researchers wrote.
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