Treatment with vutrisiran was associated with benefits across multiple well-established clinical measures of disease progression compared with the placebo in patients with transthyretin-mediated amyloidosis with cardiomyopathy.
Marianna Fontana, MD, PhD
(Credit: British Heart Foundation)
Newly published in The New England Journal of Medicine, data from the phase 3 HELIOS-B study (NCT04153149) assessing vutrisiran (Amvuttra), an FDA-approved subcutaneously administered RNA interference therapeutic agent, showed that the treatment with the medication significantly reduced the risk of death and cardiovascular events relative to placebo among patients with transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM).1
Among 655 patients randomized in the trial (vutrisiran, n = 326; placebo, n = 329), vutrisiran treatment led to a lower risk of death from any cause and recurrent cardiovascular events in both the overall population (HR, 0.72; 95% CI, 0.56-0.93; P = .01) and in the monotherapy population (HR, 0.67; 95% CI, 0.49-0.93; P = .02) in comparison with the placebo. Notably, treatment with vutrisiran also led to a lower risk of death from any cause compared with the placebo through 42 months (HR, 0.65; 95% CI, 0.46-0.90; P = .01)
“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,” lead author Marianna Fontana, MD, PhD, a professor of cardiology at University College London, said in a statement.2 “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 phase 3, double-blinded, randomized trial, investigators assigned patients with ATTR-CM 1:1 to be given vutrisiran 25-mg or placebo every 12 weeks for up to 36 months. Authors noted that the primary end point was composite of death from any cause and recurrent cardiovascular events, which the trial achieved as observed in the findings. The secondary end points for the study included death from any cause, change from baseline in the distance covered on the 6-minute walk test and in the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score. Researchers assessed efficacy end points in the overall population and in the monotherapy population, who were patients that did not receive tafamidis at baseline, and had them tested hierarchically.
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Authors reported that a primary end-point event occurred among 163 patients who were treated with vutrisiran and in 202 patients who were in the placebo group. In the overall population, treatment with vutrisiran showed less of a decline in the distance covered on the 6-minute walk test compared with placebo (least-squares mean difference, 26.5 m; 95% CI, 13.4 to 39.6; P <.001) and less of a decline in the KCCQ-OS score (least-squares mean difference, 5.8 points; 95% CI, 2.4 to 9.2; P <.001). Researchers also noted similar benefits observed among the patients in the monotherapy population.
“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, because of the progressive nature of ATTR-CM, early treatment can more effectively preserve functional capacity and quality of life,” Fontana said in a statement.2
In terms of the safety findings, investigators reported that the incidence of adverse events (AEs) was similar in both groups, showing 99% experienced AEs in the vutrisiran group and 98% experienced AEs in the placebo group. Presented at the 2024 European Society of Cardiology (ESC) Congress, held August 30-September 2, in London, United Kingdom, authors also noted that serious AEs occurred in 62% of the patients in the vutrisiran group and in 67% of patients in the placebo group.
“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,” Pushkal Garg, MD, the chief medical officer at Alnylam, said in a statement.2
“While the results have not yet been reviewed by a regulatory authority, the data we have shared today 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,” Garg added in a statement.2 “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.”
