Vutrisiran reduces composite of all-cause mortality or recurrent CV events in ATTR-CM

This summary is based on the presentation of Marianna Fontana, MD, PhD (London, UK) at the ESC Congress 2024 – Primary results from HELIOS-B, a phase 3 study of vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy.

Introduction and methods

ATTR cardiomyopathy leads to progressive heart failure, arrhythmias, decline in functional status and QoL, an increase in hospitalization and reduced survival. There is an evolution toward earlier diagnosis and improved HF management as contemporary patients have less advanced disease. Patients are managed with tafamidis, SGLT2 inhibitors and diuretics.

In the HELIOS-B study, the efficacy and safety of vutrisiran was evaluated in a contemporary ATTR-CM patient population. Vutrisiran is an SC administered RNAi therapeutic, that results in rapid knockdown of transthyretin (TTR), prevents amyloid fibril deposition. It thereby improves and stabilizes heart failure status and arrhythmia and finally reduces mortality and hospitalization. The HELIOS-B was a randomized, double-blind outcome study in ATTR amyloidosis patients with cardiomyopathy. In total, 655 patients with wild-type of any TTR variant with confirmed cardiomyopathy and history of symptomatic HF were randomized (1:1 ratio) to vutrisiran (SC q3M 25 mg) or to placebo.

The primary endpoint was the composite outcome of all-cause mortality or recurrent CV events during the double-blind period (month 33-36) in both the overall population and the monotherapy population (patients not on tafamidis at baseline). Approximately 40% of patients were on tafamidis at baseline.

Main results

• In the vutrisiran group, the outcome of recurrent CV events or all-cause mortality was reduced compared with the placebo group (HR 0.718, 95%CI: 0.555-0.929, P=0.0118), as was the outcome of first CV event or all-cause mortality (HR 0.716, 95%CI: 0.566-0.905, P=0.0062).
• All-cause mortality was reduced in the vutrisiran group compared with the placebo group (HR 0.645, 95%CI:0.463-0.898, P=0.0098).
• The median change over time in 6-MWT was less in the vutrisiran group compared with the placebo group (LSMD 26.46 m, 95%CI: 13.38-39.55, P=0.00008).
• Similar, the median change over time in KCCQ-OS was less in the vutrisiran group compared with the placebo group (LSMD 5.80, 95%CI: 2.40-9.20, P=0.0008).
• Subgroup analyses by age, baseline tafamidis use, ATTR disease type, NYHA class, baseline NT-proBNP showed similar treatment effects of vutrisiran.
• The safety and tolerability profiles was acceptable, as previously established.

Conclusion

In the HELIOS-B study, treatment with vutrisiran reduced the composite endpoint of all-cause mortality or recurrent CV events in a contemporary population with ATTR-CM, including substantial use of background therapy. In addition to the primary endpoint, vutrisiran achieved statistical significance on all secondary endpoints, including 6-MWT, KCCQ-OS and NT-proBNP.

Fontana ended her presentation by saying that vutrisiran has the potential to become the standard of care for newly diagnosed patients and those progressing on stabilizing therapies.

- Our reporting is based on the information provided at the ESC Congress 2024 -

The findings of this study were simultaneously published in N Engl J Med.