For East Asian patients with ATTR-CM, Amvuttra is safe, extends survival
Analysis confirms therapy's effectiveness for patient group in global clinical trial
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For East Asian adults with transthyretin amyloid cardiomyopathy (ATTR-CM), the approved therapy Amvuttra (vutrisiran) is a safe and effective treatment, with significant long-term benefits.
Those are the findings of a new data analysis from the Phase 3 HELIOS-B study (NCT04153149), a global clinical trial designed to assess the treatment’s effects over nearly three years in more than 650 people with ATTR-CM. This subgroup analysis specifically looked at Amvuttra use among participants from South Korea and Japan.
The results showed that Amvuttra significantly reduced mortality and recurrent cardiovascular, or heart-related, events relative to a placebo for East Asian patients with the progressive condition, which is characterized by accumulating heart damage. Treatment was also linked to trends of improved quality of life and smaller increases in heart damage biomarkers.
These benefits were seen regardless of whether patients were also receiving Vyndamax (tafamidis) — an older ATTR-CM-approved therapy — and were similar to those previously reported in the overall study population.
“The consistency of treatment effects observed in this subpopulation, including … clinical response, and safety profile, provides early support for the suitability of [Amvuttra] in East Asian clinical settings,” the researchers wrote.
The study, “Vutrisiran in East Asian Patients With Transthyretin Amyloidosis With Cardiomyopathy: Post-Hoc Analysis of HELIOS-B,” was published in JACC: Asia. It was funded by Alnylam Pharmaceuticals, which markets Amvuttra; two study authors are employed by the company.
Amvuttra is now approved in Japan — and in the U.S. and the European Union — for the treatment of ATTR-CM. In South Korea, Amvuttra is not approved for treating ATTR-CM, though it is cleared for use in a related condition.
ATTR-CM is characterized by the formation of toxic clumps of a misfolded version of the transthyretin (TTR) protein that primarily accumulate in the heart. This can impair heart function, reduce exercise capacity, and eventually lead to heart failure.
The disease is typically caused by either genetic mutations in the TTR gene, when it’s called hereditary ATTR-CM, or by aging-related processes, known as wild-type.
ATTR-CM historically underdiagnosed in East Asian nations
In recent years, both types have been increasingly diagnosed among people in Asian nations.
“Historically, ATTR-CM has been underdiagnosed in East Asian countries, but increased awareness and access to noninvasive diagnostic tools over the past decade have led to a growing number of diagnoses,” the researchers wrote.
The HELIOS-B trial included study sites in both South Korea and Japan, as well as Malaysia and Thailand. Overall, the study tested Amvuttra at 119 locations worldwide.
As an RNA interference therapy, Amvuttra contains a piece of genetic material designed to ultimately lower the production of TTR protein, which is expected to prevent the formation of toxic clumps and their associated damage.
Administered through a subcutaneous, or under-the-skin, injection once every three months, Amvuttra is now approved for treating adults with ATTR-CM and those with hereditary transthyretin amyloidosis with polyneuropathy, a related disease that mainly affects certain nerve cells.
Regulatory approvals of Amvuttra for ATTR-CM were based on data from the HELIOS-B trial, which tested Amvuttra against a placebo for up to three years in 654 adults with hereditary or wild-type ATTR-CM who had a clinical history of heart failure.
Data showed that the treatment significantly reduced the risk of a composite measure of death due to any cause (all-cause mortality) and recurrent cardiovascular events, including heart-related hospitalizations and urgent heart failure visits, compared with the placebo. Amvuttra also preserved patients’ functional capacity and quality of life.
Similar benefits were seen among participants not receiving Vyndamax at the study’s start, meaning they were treated with Amvuttra alone.
Amvuttra benefits seen for patients in Japan, South Korea
Now, a team of researchers assessed Amvuttra’s safety and efficacy in the subgroup of 32 HELIOS-B participants enrolled in Japan and South Korea.
As in the whole trial population, the East Asian participants had a median age older than 70, were mainly men, and most commonly had wild-type ATTR-CM. For most, the disease mildly affected physical activity, as indicated by a New York Heart Association (NYHA) class II.
The researchers noted that the East Asian subgroup had higher rates of NYHA class II, but lower rates of Vyndamax use compared with the overall study population.
Among East Asian patients, Amvuttra significantly reduced the risk of the composite measure of all-cause mortality and recurrent cardiovascular events relative to the placebo. Similar effects were seen in participants treated with Amvuttra alone.
In East Asian patients with ATTR-CM from HELIOS-B, the efficacy and safety of [Amvuttra] were consistent with the overall population.
In addition to this main outcome measure, East Asian participants treated with Amvuttra showed trends of smaller reductions in functional capacity and greater improvements in quality of life relative to those on the placebo. Also, a slightly greater proportion of Amvuttra-treated patients maintained or improved their NYHA class, reflecting preserved physical activity.
Amvuttra was also associated with smaller increases in blood levels of heart damage biomarkers (NT-proBNP and troponin I) and substantial and consistent reductions in blood TTR levels compared with the placebo. This is consistent with trends seen across the full trial population.
“The safety and tolerability profile of [Amvuttra] in the East Asian subpopulation was consistent with that of the overall HELIOS-B population,” the researchers wrote, with similar rates of adverse events and serious adverse events in the Amvuttra and placebo groups.
The most frequently reported adverse events involved the heart, reflecting the underlying disease burden rather than treatment-related events. Still, East Asian participants on Amvuttra were more likely to experience heart failure (24% vs. 13%) and fast heart rate (12% vs. 0%) than those on the placebo.
“In East Asian patients with ATTR-CM from HELIOS-B, the efficacy and safety of [Amvuttra] were consistent with the overall population,” the researchers wrote, adding that noting “this is the first published report of an RNA interference treatment for ATTR-CM in patients from East Asia.”
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