Heart drug Attruby might also safeguard kidney function
Clinical trial data reveal unique organ protection benefits for ATTR-CM
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Attruby (acoramidis), an approved therapy for transthyretin amyloid cardiomyopathy (ATTR-CM), may help preserve kidney function in adults with the rare heart disease, potentially lowering their risk of early cardiovascular events, according to a new analysis of clinical trial data.
“Kidney dysfunction is pervasive in this population and an independent predictor of mortality from ATTR-CM,” Jeffrey Testani, MD, the study’s first author at Yale School of Medicine, said in a press release from Bridgebio, the company that sells Attruby in the U.S. The oral therapy “appears to have a protective effect on the heart and the kidney simultaneously, with potentially meaningful implications for long-term survival and reduced cardiovascular hospitalizations.”
The study, “Effects of Acoramidis on Kidney Function in Transthyretin Amyloid Cardiomyopathy,” was published in Circulation: Heart Failure. It was sponsored by Bridgebio. Outside the U.S., the therapy is sold by Bayer under the brand name Beyonttra.
Heart and kidney connections
“For a patient population that is older, sicker, and increasingly surviving long enough for organ preservation to matter, these cardiorenal [heart-and-kidney] observations represent an important advancement in the care of patients living with ATTR-CM,” Testani said.
The findings suggest that, in addition to its known effects on heart health, Attruby might also directly affect kidney health through biological mechanisms that remain unclear. “Additional investigation is needed to further explore the mechanism(s) and therapeutic implications of these observations,” the researchers wrote.
ATTR-CM is marked by the production of a faulty transthyretin protein that is prone to forming toxic clumps that damage the heart.
Attruby is an oral treatment that works by stabilizing the transthyretin protein, preventing these aggregates from forming. It is approved to reduce cardiovascular death and cardiovascular-related hospitalization in adults with ATTR-CM.
In clinical trials, it was shown to reduce the risk of death from any cause and cardiovascular-related hospitalization, as well as improve functional capacity and quality of life. During Attruby’s development program, researchers observed an early, modest reduction in estimated glomerular filtration rate (eGFR), a measure of kidney function, upon initiation of therapy.
Because kidney and heart health are intimately connected, a team of researchers conducted a comprehensive analysis of these changes in kidney function to understand their potential clinical implications.
The analysis included data from more than 600 ATTR-CM patients in the Phase 3 ATTRibute-CM trial (NCT03860935) and its open-label extension study (NCT04988386), as well as dozens of patients in an earlier Phase 2 study (NCT03458130) and its open-label extension (NCT03536767).
Participants in the main trials were randomly assigned to receive Attruby or a placebo, and then moved to the extension studies, where all received long-term Attruby treatment. Data from these studies, mainly ATTRibute-CM, formed the basis of the therapy’s regulatory approvals.
In the new study, the researchers specifically examined two kidney function measures: eGFR and the urinary albumin-to-creatinine ratio (UACR). While eGFR measures how efficiently the kidneys filter blood, with higher values generally indicating better kidney function, UACR looks at the ratio of two kidney health markers in urine, with lower values indicating better kidney health.
The researchers found that, across the trials, Attruby initiation was associated with a rapid, modest reduction in eGFR that was reversed when treatment was stopped. While lower eGFR values usually indicate worse kidney function, the observed drop was accompanied by a decrease in UACR, suggesting improved overall kidney health.
Furthermore, statistical analyses showed that patients with a larger eGFR dip at the start of therapy were significantly less likely to die or be hospitalized due to heart health problems over the course of follow-up.
Long-term kidney preservation
Even though eGFR declined immediately after starting Attruby, over the long term, the rate of eGFR decline was significantly slower in participants receiving Attruby than in those on the placebo. These data imply that long-term Attruby treatment may help preserve kidney function.
Further supporting that idea, observed changes in kidney function measures with Attruby were not associated with an increased risk of kidney health problems. In fact, across the studies, three participants died due to kidney problems, and all of them had been given the placebo.
Some trial participants also received Vyndamax (tafamidis), another ATTR-CM-approved treatment that stabilizes the transthyretin protein. Use of Vyndamax had no apparent impact on kidney health markers, suggesting that Attruby’s effects on kidney function likely occur through transthyretin-independent mechanisms.
“We observed early and sustained cardiorenal benefits of [Attruby] treatment with a pattern similar to what we see with drugs [that are currently used to preserve kidney health], suggesting [Attruby] may have a direct effect on kidney function,” Testani said. “These effects have not been reported with other ATTR-CM medications.”
The researchers stressed that the trials used for this analysis were not designed to measure Attruby’s effects on kidney function, so the results should be considered exploratory pending future studies. Still, they said their findings should encourage additional research into how Attruby may affect kidney health.
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