Acoramidis Improves Cardiovascular Outcomes by Increasing Serum Transthyretin: Phase 3 Study Results

BridgeBio Pharma, Inc., a biopharmaceutical company dedicated to genetic diseases and cancer, recently announced promising Phase 3 trial results for its drug acoramidis in treating transthyretin amyloid cardiomyopathy (ATTR-CM). These findings, presented at the 2024 International Symposium of Amyloidosis (ISA), highlight acoramidis' impact on clinical outcomes, including mortality and hospitalization rates.

ATTR-CM is a serious condition caused by the buildup of amyloid proteins in the heart, leading to heart failure and other complications. BridgeBio's acoramidis, an orally administered small molecule, aims to stabilize transthyretin (TTR), a protein that misfolds and forms amyloid deposits. The Phase 3 ATTRibute-CM study was designed to assess acoramidis' efficacy and safety in this context.

One key insight from the study is that acoramidis treatment increased serum TTR levels as early as Day 28, and these elevated levels were maintained through Month 30. This increase was linked to a reduced risk of all-cause mortality (ACM), cardiovascular mortality (CVM), and cardiovascular-related hospitalization (CVH). The correlation between higher serum TTR levels and improved clinical outcomes was significant, offering hope for better management of ATTR-CM.

In detail, for every 5mg/dL increase in serum TTR at Day 28, the risk of death by Month 30 dropped by around 30%, according to statistical models. Additionally, a 1mg/dL increase in TTR was associated with a 5.5% reduction in cardiovascular deaths and a 4.7% decrease in CVH risk. These findings are the first to prospectively demonstrate the relationship between changes in serum TTR and subsequent clinical outcomes in ATTR-CM patients.

The ATTRibute-CM trial also revealed early benefits of acoramidis. By Month 3, patients showed a significant reduction in a composite endpoint of CVM and CVH, with a 15.2% absolute risk reduction and a 38.2% hazard reduction by Month 30. These benefits were presented in Kaplan-Meier curves, which displayed early and sustained treatment advantages.

Further analysis indicated that patients who had at least one CVH during the study had a notably higher mortality risk. Specifically, patients without CVH during the trial had an 86.7% survival rate at 30 months, compared to 60.1% for those with at least one CVH. This suggests that reducing CVH risk is crucial for improving long-term outcomes in ATTR-CM patients.

BridgeBio also discussed the upcoming ACT-EARLY trial, which will be the first Phase 3 study aimed at preventing or delaying ATTR amyloidosis in asymptomatic carriers of pathogenic TTR variants. This trial is expected to start later in 2024 and underscores the company's commitment to expanding therapeutic options for ATTR-CM.

Dr. Jonathan Fox, President and Chief Medical Officer of BridgeBio Cardiorenal, emphasized the significance of these findings, stating that the comprehensive data on acoramidis, including clinical outcomes, biomarkers, quality of life, and cardiac imaging, continue to grow. He expressed optimism about the potential benefits of targeting near-complete TTR stabilization and the resulting increases in serum TTR, which could lead to significant clinical improvements for patients.

BridgeBio has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration, which has been accepted with a Prescription Drug User Fee Act (PDUFA) action date set for November 29, 2024. Additionally, a Marketing Authorization Application (MAA) has been submitted to the European Medicines Agency, with a decision anticipated in 2025.

In conclusion, the recent analyses from the ATTRibute-CM study provide robust evidence of acoramidis' potential to significantly improve outcomes for ATTR-CM patients. With the upcoming ACT-EARLY trial and regulatory submissions underway, BridgeBio is poised to make a substantial impact on the treatment landscape for this challenging disease.