Amvuttra may ease symptoms and improve daily life in ATTR-CM
Trial data show gains in quality of life and physical function
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Amvuttra (vutrisiran) was associated with improvements in quality of life and physical function in adults with transthyretin amyloidosis with cardiomyopathy (ATTR-CM).
That’s according to new data from HELIOS-B (NCT04153149), the Phase 3 clinical trial that supported Amvuttra’s approval for adults with ATTR-CM. Additional analyses of patients with advanced disease and those with a heart problem called diastolic dysfunction also showed benefits in outcomes such as mortality and cardiovascular events. These findings were recently presented at the American College of Cardiology’s Annual Scientific Session and Expo.
New analyses highlight benefits across disease severity
“These new data present further evidence of the meaningful impact [Amvuttra] offers patients with ATTR‑CM and provide deeper insight into its benefits for patients with more advanced disease,” Ronald Witteles, MD, a professor at Stanford University School of Medicine and a HELIOS-B investigator, said in a press release from Alnylam Pharmaceuticals, which markets Amvuttra.
The trial’s quality of life data were published in the European Journal of Heart Failure under the title “Effect of vutrisiran on components of health status in transthyretin amyloidosis with cardiomyopathy: the HELIOS-B study.” These findings show improvements in several measures of health status, including quality of life and physical limitations.
ATTR-CM is a type of amyloidosis, a group of diseases in which toxic protein clumps accumulate in the body’s tissues, causing damage. In ATTR-CM, these aggregates are made of a misfolded transthyretin protein and can be caused either by genetic mutations in the TTR gene (hereditary) or by aging (wild-type).
Because transthyretin clumps in ATTR-CM tend to accumulate in the heart, symptoms include abnormal or fast heart rate, shortness of breath, fatigue, and swelling in the feet and ankles.
Amvuttra contains a piece of genetic material that reduces the production of TTR, helping to lower levels of the protein that form toxic clumps and slow disease progression. It is approved in the U.S. and Europe for ATTR-CM, both hereditary and wild-type forms, and for hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), another type of transthyretin-related amyloidosis.
HELIOS-B trial evaluated Amvuttra in ATTR-CM
The HELIOS-B trial included 654 adults with hereditary or wild-type ATTR-CM who had a clinical history of heart failure. Participants received subcutaneous (under-the-skin) injections of either Amvuttra or a placebo every three months for about three years. Those who completed the study period were eligible to enter an open-label extension, where they could receive Amvuttra for up to two additional years.
A total of 486 participants had Kansas City Cardiomyopathy Questionnaire (KCCQ) data available at both the start of the study and at 30 months, which measures symptoms of heart failure and how they affect daily life. Most of these patients were men (93%) and had wild-type ATTR-CM (91%), with a mean age of 75.
After 30 months (about 2.5 years), Amvuttra-treated patients showed more favorable changes across nearly all areas of the questionnaire compared with those on the placebo. The therapy showed the greatest benefits in activities such as hurrying or jogging and walking on level ground, as well as feeling less discouraged by their condition.
In patients not on Vyndamax (tafamidis), an approved therapy for ATTR-CM, at the start of HELIOS-B, Amvuttra “showed the larger improvement compared with placebo in KCCQ items related to domains of physical limitations, social limitations, and quality of life, and items of burden and frequency in shortness of breath,” the researchers wrote.
Also, after 30 months, the difference in KCCQ scores between patients treated with Amvuttra and those given the placebo “was estimated to correspond to a difference of approximately 11 years of age,” the team wrote.
Analysis examines outcomes in patients with advanced disease
Another analysis focused on HELIOS-B participants with advanced disease, defined using the New York Heart Association (NYHA) scale, where higher classes mean more severe symptoms.
In the overall patient population, fewer patients taking Amvuttra developed advanced disease compared with those on the placebo (8% vs. 10.7%). Among those who did, Amvuttra was found to significantly reduce the risk of death or repeated cardiovascular events by about 40% in the overall analysis.
Among these patients with advanced disease, the therapy also reduced the risk of death by 56% overall and by 77% when used alone during the three-year placebo-controlled period plus up to six months of treatment in the extension portion. Rates of adverse events were reported to be similar or lower among patients given Amvuttra.
“[Amvuttra] not only meaningfully reduced the risk of progression to advanced disease, but among patients who did progress, it demonstrated compelling improvements in both cardiovascular outcomes and survival,” said Witteles, who also co-directs the Stanford Amyloid Center. “These findings provide important evidence to help inform treatment decisions for the highest-risk ATTR‑CM patients.”
Separate analysis looks at patients with diastolic dysfunction
A separate analysis showed that trial participants with more severe diastolic dysfunction, when the heart’s lower chambers become stiff and fail to relax properly during the blood-filling phase, had poorer outcomes.
However, Amvuttra allowed more patients with the most severe diastolic dysfunction to remain stable or improve in their NYHA class (70.8% vs. 55.6%). The therapy also reduced the risk of death and cardiovascular events during the study period, regardless of baseline diastolic dysfunction severity.
Newly presented real-world data also supported Amvuttra’s use in clinical practice. Over an average of 613.8 days (about 1.7 years), most patients (93.8%) adhered to treatment, meaning they took it as prescribed (defined as coverage of at least 80% of days). In this analysis, persistence was also high, with most patients still on treatment after one year.
