Acoramidis Demonstrates Long-Term Benefits in ATTR-CM: Results from the ATTRibute-CM Open-Label Extension

Promising long-term outcomes from the ongoing Open-Label Extension (OLE) of the ATTRibute-CM trial highlight the efficacy of acoramidis, an investigational therapy for transthyretin cardiac amyloidosis (ATTR-CM). Presented at the 2024 AHA Scientific Sessions, the study underscores acoramidis’ significant reductions in all-cause mortality (ACM) and cardiovascular hospitalizations (CVH), reinforcing its potential as a transformative therapy for this progressive disease.

ATTR-CM results from transthyretin protein misfolding, leading to cardiac dysfunction and heart failure. Acoramidis is a next-generation TTR stabilizer achieving ≥90% stabilization in clinical trials. The Phase 3 ATTRibute-CM trial previously demonstrated significant reductions in ACM, CVH, and improvements in biomarkers and functional outcomes over 30 months. This ongoing OLE investigates acoramidis’ long-term effects over 36 and 42 months.

Participants completing the ATTRibute-CM trial were enrolled in the OLE and received 800 mg acoramidis hydrochloride twice daily. The study employed Cox proportional hazards models to evaluate time-to-first event analyses for ACM, the composite of ACM or first CVH, and first CVH alone. An Andersen-Gill analysis assessed recurrent ACM and CVH events.

The OLE findings demonstrate continued and significant benefits:

• Compared to placebo, acoramidis reduced ACM by 35.7% and 33.7% at 36 and 42 months, respectively (p<0.01 for both).
• Composite ACM and first CVH were reduced by 34.3% at 36 months and 33.9% at 42 months (both p<0.0001).
• First CVH alone was reduced by 40.5% at 36 months and 41.0% at 42 months (both p<0.0001).
• Recurrent events (ACM and CVH) showed a 34% and 39% reduction at 36 and 42 months, respectively (both p<0.0001).

The safety profile of acoramidis remains consistent with the parent trial.

 Takeaways

These results affirm acoramidis’ durable benefits in reducing mortality and hospitalizations for ATTR-CM patients, with trends suggesting improved survival in patients who transitioned from placebo to acoramidis. The findings highlight the importance of early and sustained treatment for achieving optimal outcomes in ATTR-CM management. With its strong safety profile and significant clinical efficacy, acoramidis represents a major advance in treating transthyretin cardiac amyloidosis.

Reference

Judge D, Gilmore J, Alexander K, et al. Acoramidis Reduces All-Cause Mortality (ACM) and Cardiovascular-Related Hospitalization (CVH): Initial Outcomes From the ATTRibute-CM Open-Label Extension (OLE) Study. Presentation #4172052. Presented at the American Heart Association Scientific Sessions 2024; November 16-18, Chicago, Illinois.