Starting Attruby early cuts heart-related risks by half in ATTR-CM
Long-term use of approved therapy safely extends patient survival, data show
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Starting Attruby (acoramidis) early and taking it continuously helps adults with transthyretin amyloid cardiomyopathy (ATTR-CM) live longer, stay out of the hospital for cardiovascular problems, and keep their heart function more stable over time.
That’s according to 4.5 years of pooled data from the now-completed Phase 3 ATTRibute-CM clinical trial (NCT03860935) and its ongoing open-label extension (OLE) study (NCT04988386). The trial had enrolled more than 600 people with the progressive heart condition.
The researchers noted that benefits from the approved oral therapy were seen in individuals with both hereditary and nonhereditary, or wild-type, forms of the disease.
“These findings support the importance of early and continuous long-term treatment with [Attruby] in ATTR-CM,” the scientists wrote.
The results were described in “Long-Term Durability of Acoramidis Efficacy in Transthyretin Amyloid Cardiomyopathy: Open-Label Extension of the ATTRibute-CM Randomized Clinical Trial,” a study published in the journal JAMA Cardiology. The work was funded by Attruby’s developer Bridgebio.
ATTR-CM occurs when the protein transthyretin (TTR) breaks down, misfolds, and clumps into toxic clumps or aggregates, called amyloid fibrils, that accumulate mainly in the heart muscle. This causes thickening and stiffening of the heart walls, reducing the organ’s ability to pump blood and leading to symptoms such as shortness of breath and an irregular heartbeat.
The disease can be classified as hereditary, when it’s caused by mutations in the TTR gene, or wild-type, which seems to develop sporadically with older age.
Attruby designed to slow disease, ease symptoms
TTR stabilizers such as Attruby are designed to bind directly to the TTR protein and help keep it stable, preventing it from breaking apart. This reduces the formation of amyloid deposits, easing symptoms and slowing disease progression.
The therapy is taken twice daily in the form of oral tablets. It is marketed by BridgeBio in the U.S., and by Bayer in Europe, under the brand name Beyonttra.
Its regulatory approvals for use in reducing cardiovascular-related hospitalizations or death in adults with hereditary or wild-type ATTR-CM were based on data from the Phase 3 ATTRibute-CM study. Data at 30 months, or about 2.5 years, demonstrated that Attruby was superior to a placebo at prolonging survival and improving heart-related outcomes.
Of the 632 participants randomly assigned to receive either Attruby or a placebo in ATTRibute-CM, 389 entered the OLE study, in which they are treated with Attruby for up to five years.
Among those continuing in the extension, 263 took Attruby continuously from ATTRibute-CM’s start and were thus dubbed the continuous treatment group. The remaining 126 were originally assigned to the placebo and switched to Attruby upon entering the OLE study. This second group was call the switch group by researchers.
Previous pooled data from ATTRibute-CM and its OLE study showed that Attruby’s benefits were sustained for as long as 3.5 years regardless of what caused the ATTR-CM, how old the patients were, or how severe were their symptoms.
Patients at advanced stages can still benefit, data show
Now, the researchers described new pooled trial data collected over a longer period of time, specifically 54 months or about 4.5 years, in both studies.
Among the main goals was to watch for differences in time to death from any cause between the continuous treatment and switch groups. Other main endpoints were time to death from cardiovascular causes, and time to a first hospitalization due to cardiovascular problems The researchers also monitored safety.
The results showed that continuous Attruby treatment cut the rate of all evaluated outcomes by about half compared with a delayed treatment start. Death from any cause occurred in 26% of patients who took Attruby from ATTRibute-CM’s start and in 44% of those who switched from the placebo.
Early, continuous Attruby treatment was also associated with lower rates of cardiovascular-related death (19% vs. 34%) and hospitalization due to cardiovascular problems (35% vs. 57%).
Statistical models demonstrated that early Attruby treatment reduced the risk of all-cause death by 45%, cardiovascular-related death by 49%, and cardiovascular-related hospitalization by 47%.
These findings demonstrate the long-term, sustained clinical benefits of [Attruby] in ATTR-CM and emphasize the need for early diagnosis followed by prompt treatment in patients with ATTR-CM, … while recognizing that patients presenting at an advanced stage may still benefit.
Survival benefits were seen across different subgroup of patients, but included individuals with hereditary or wild-type ATTR-CM and those with earlier or more advanced disease stage.
Early, continuous treatment with Attruby also kept NT-proBNP, a marker of heart strain, largely stable over 54 months, showing a slightly increase of 40%, while levels increased by 149% in the switch group.
Patients in either group showed an increase in circulating TTR levels about one month after starting Attruby, which suggests that the protein was not accumulating as much in tissues. While this increase was generally maintained through month 54 in both groups, it was larger in the continuous treatment group, resulting in higher circulating TTR levels at last follow-up.
Quality of life, as assessed with the Kansas City Cardiomyopathy Questionnaire-Overall Summary, remained more stable with continuous treatment, and physical function, measured by the six-minute walk distance test, declined less, the data showed.
No new side effects appeared over the longer follow-up, suggesting that Attruby may remain safe even when taken for several years.
“These findings demonstrate the long-term, sustained clinical benefits of [Attruby] in ATTR-CM and emphasize the need for early diagnosis followed by prompt treatment in patients with ATTR-CM,” the researchers concluded, “while recognizing that patients presenting at an advanced stage may still benefit.”
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