BridgeBio reports new Circulation: Heart Failure analyses showing acoramidis provided early and sustained kidney protection alongside cardiovascular benefits in patients with ATTR-CM.
Written By: Farha Farheen, Pharm D
Reviewed By: Pharmacally Editorial Team
BridgeBio Pharma has reported new evidence indicating that acoramidis may provide direct kidney protection in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), alongside its established transthyretin (TTR) stabilization activity. The findings, published in Circulation: Heart Failure, are based on post-hoc analyses of the randomized, double-blind, placebo-controlled Phase 2 trial and the Phase 3 ATTRibute-CM study (NCT03860935).
The analyses showed that treatment with acoramidis produced an early, reversible decline in estimated glomerular filtration rate (eGFR), followed by sustained improvements in kidney function and reductions in urinary albumin excretion through 30 months. Researchers suggest this pattern resembles the hemodynamic response seen with established kidney-protective therapies such as ACE inhibitors, angiotensin receptor blockers (ARBs), and SGLT2 inhibitors, a profile not previously reported with other approved ATTR-CM treatments.
Kidney protection may extend beyond TTR stabilization
ATTR-CM is a progressive disease caused by misfolded transthyretin proteins that accumulate in the heart, leading to heart failure, reduced quality of life, and premature death. Kidney dysfunction is common in these patients and independently predicts worse survival and cardiovascular outcomes.
Acoramidis is an orally administered, selective small-molecule TTR stabilizer that achieves near-complete (≥90%) stabilization of transthyretin. The new analyses suggest its clinical effects may extend beyond TTR stabilization by directly influencing renal hemodynamics.
Within 28 days of treatment initiation, acoramidis produced a reversible 8.5 mL/min/1.73 m² decline in eGFR while reducing urinary albumin-to-creatinine ratio (UACR) by 15.5% versus placebo (P<0.05). No kidney-related adverse events were reported during these analyses.
Long-term improvements in kidney function accompanied cardiovascular benefit
The analyses also demonstrated a significantly improved chronic eGFR slope of +2.47 mL/min/1.73 m² per year (P<0.001) and a sustained 13.7% reduction in UACR through Month 30 (P=0.026), suggesting durable preservation of kidney function.
Investigators further explored whether the early eGFR decline carried clinical significance. Patients experiencing larger-than-median initial eGFR reductions had a 58% lower risk of death or cardiovascular hospitalization during the first treatment year (HR 0.42; 95% CI 0.22-0.78; P=0.006). They also experienced a 66% lower risk of cardiovascular hospitalization alone (HR 0.34; 95% CI 0.17-0.66; P=0.002). In contrast, participants receiving placebo who developed similar eGFR declines experienced poorer clinical outcomes.
Lead author Jeffrey Testani, MD, MTR, of Yale School of Medicine, said the findings suggest acoramidis may simultaneously protect both the heart and kidneys. Given the high prevalence of kidney impairment in ATTR-CM, preserving renal function could contribute to improved long-term survival and fewer cardiovascular hospitalizations.
Regulatory status
Acoramidis is marketed as Attruby® in the United States following FDA approval for ATTR-CM and as BEYONTTRA® in multiple international markets, including the European Union, Japan, Switzerland, the United Kingdom, and Brazil. The newly published analyses strengthen the understanding of the drug’s clinical profile and support further investigation into its potential kidney-specific mechanism of action beyond transthyretin stabilization.
What This Means for Patients
For people living with ATTR-CM, heart and kidney health are closely connected. As the disease progresses, declining kidney function can increase the risk of hospitalization, worsen heart failure, and reduce survival.
These new findings suggest that acoramidis may help protect the kidneys as well as the heart. Although patients experienced a small drop in kidney function soon after starting treatment, researchers found that this change was temporary and was followed by better long-term kidney function. Patients taking acoramidis also had lower levels of protein in their urine, an important sign of healthier kidneys.
Researchers believe these benefits of kidney explain why acoramidis showed earlier reductions in cardiovascular events in previous studies. While these results come from post-hoc analyses and require further confirmation, they provide encouraging evidence that acoramidis may offer broader protection for patients with ATTR-CM by supporting both heart and kidney health over time.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.