Detailed results from the positive HELIOS-B phase III study of vutrisiran in patients with ATTR amyloidosis with cardiomyopathy presented at the European Society of Cardiology Congress.-Alnylam Pharmaceuticals

The data were presented in a Hot Line session at the European Society of Cardiology (ESC) Congress 2024, taking place August 30-September 2 in London, United Kingdom. Results from the HELIOS-B study were also simultaneously published in The New England Journal of Medicine. As previously reported, the HELIOS-B study met all 10 of its primary and secondary endpoints, across both the overall and monotherapy populations, with statistical significance.

Enrolled patients were predominantly New York Heart Association (NYHA) Class I or II with wild-type disease and had been diagnosed by non-invasive methods, with substantial concurrent treatment with available standard of care treatments such as tafamidis and SGLT2 inhibitors – reflecting the contemporary ATTR-CM patient population.

In the study, treatment with vutrisiran substantially reduced the risk of death and cardiovascular events relative to placebo. In the overall population, vutrisiran reduced the risk of all-cause mortality and recurrent cardiovascular events by 28%, with similar reductions in both the mortality and cardiovascular events components of the endpoint. Mortality in this population was significantly reduced by 31% during the double-blind period and by 36% up to 42 months. In the monotherapy population, vutrisiran significantly reduced the risk of all-cause mortality and recurrent cardiovascular events by 33% and significantly reduced the risk of mortality by 35% up to 42 months. As a component of the primary endpoint, a non-significant reduction of 30% in mortality was observed (nominal p-value 0.1179) in the monotherapy population during the double-blind period.

Vutrisiran treatment was also associated with benefits versus placebo across multiple well-established clinical measures of disease progression, including 6-Minute Walk Test, Kansas City Cardiovascular Questionnaire, and NYHA Class, as well as the cardiac biomarker NT-proBNP. Subgroup analyses demonstrated consistent benefits across all key patient segments, including patients receiving background tafamidis. Trends toward greater efficacy were seen in patients with earlier disease (i.e., younger patients and those with lower baseline NT-proBNP).

In HELIOS-B, the safety and tolerability profiles of vutrisiran were consistent with what had been established in the currently approved patient population, as well as earlier clinical studies.

“Results from the HELIOS-B study demonstrate a significant advance in the treatment of ATTR amyloidosis with cardiomyopathy, suggesting that knockdown of TTR production with vutrisiran can dramatically reduce all-cause mortality and cardiovascular events,” said Marianna Fontana, M.D., Ph.D., HELIOS-B investigator, Professor of Cardiology, University College London, National Amyloidosis Center, Royal Free Hospital, London. “Over the past decade, advances in ATTR-CM have led to more patients being diagnosed earlier in their disease, often with less severe symptoms and better prognosis, as well as receiving more robust background standards of care. In this contemporary setting, the bar was high to demonstrate benefit. These HELIOS-B data also suggest that, within this current patient population, vutrisiran may provide greater benefit to patients in earlier stages of the disease where, due to the progressive nature of ATTR-CM, early treatment can more effectively preserve functional capacity and quality of life.”

“We’re proud to share the detailed HELIOS-B data with the cardiology community at the ESC Congress 2024. With this study, we have demonstrated that the rapid knockdown of toxic TTR seen with vutrisiran improves survival, and reduces cardiovascular hospitalizations and disease progression versus placebo, with benefits consistently observed across populations and regardless of background stabilizer use,” said Pushkal Garg, M.D., Chief Medical Officer of Alnylam. “While the results have not yet been reviewed by a regulatory authority, the data we have shared suggest that vutrisiran has the potential to become a new standard of care treatment for ATTR-CM, a progressive and ultimately fatal disease with limited treatment options. We want to thank everyone who contributed to the success of this study, including the patients, caregivers, investigators, study staff and my Alnylam colleagues. In light of these data, we are working with urgency to file these data with regulators and bring this medicine to patients around the world.”

See- "Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy"- Authors: Marianna Fontana, M.D., Ph.D. , John L. Berk, M.D., Julian D. Gillmore, M.D., Ph.D., Ronald M. Witteles, M.D., Martha Grogan, M.D., Brian Drachman, M.D., Thibaud Damy, M.D., Ph.D., +30, for the HELIOS-B Trial Investigators. DOI: 10.1056/NEJMoa2409134.