New analyses back Amvuttra as first-line treatment for complex heart cases
Injectable therapy shows consistent benefits across high-risk ATTR-CM groups
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New analyses back the use of the approved therapy Amvuttra (vutrisiran) as an initial treatment for people with transthyretin amyloidosis with cardiomyopathy (ATTR-CM) who have risk factors such as abnormal heart rhythms or low blood pressure.
The injectable therapy was found to lower the risk of death or recurrent cardiovascular events — acute, sudden incidents causing injury to the heart or brain, primarily due to interrupted blood flow — among ATTR-CM patients with these issues.
That’s according to a new examination of data from the Phase 3 HELIOS-B clinical trial (NCT04153149), which tested Amvuttra against a placebo in more than 600 adults with ATTR-CM. These and other results were presented earlier this month at the Heart Failure 2026 congress, held by the Heart Failure Association of the European Society of Cardiology.
“Taken together, these findings support the use of [Amvuttra] as a first-line treatment option for ATTR-CM across a broad range of patient populations,” Scott Solomon, MD, a professor at Harvard Medical School, said in a press release from Alnylam Pharmaceuticals, which markets Amvuttra.
In ATTR-CM, a protein called transthyretin forms toxic clumps that damage heart tissue. Amvuttra, which is administered by subcutaneous, or under-the-skin, injection every three months, works to reduce transthyretin levels.
The therapy is approved for ATTR-CM and hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN), a related disease marked instead by nerve damage. Approvals for ATTR-CM were mainly based on HELIOS-B top-line data, which showed a significantly reduced risk of death or major heart-related medical visits with the therapy’s use.
Additional results have also demonstrated that Amvuttra eased ATTR-CM symptoms and improved patients’ quality of life.
New analyses focused on original HELIOS-B trial data
About two-thirds of the participants in HELIOS-B had atrial fibrillation, a type of abnormal heart rhythm that’s associated with more advanced ATTR-CM disease. The newly presented analyses show that, in this population, treatment with Amvuttra significantly reduced the risk of death and recurrent cardiovascular events compared with the placebo.
Treatment effects were also seen in participants with low systolic blood pressure (when the heart pumps blood out) — a risk factor for poorer outcomes — and these patients saw their systolic blood pressure decline slowly over time.
These new HELIOS-B analyses show that the clinical benefits of [Amvuttra] were maintained across these clinically complex patient groups, as well as in patients receiving background therapies, … reinforcing both the consistency of the treatment effect and its relevance in real-world clinical practice.
Amvuttra was also effective regardless of sex, coexisting conditions, and simultaneous use of other medications. This included other approved ATTR-CM therapies, such as Vyndamax (tafamidis), and heart failure medications.
Because women have historically been underrepresented in ATTR-CM trials, the fact that Amvuttra was also effective in women is noteworthy, according to Alnylam.
“These new HELIOS-B analyses show that the clinical benefits of [Amvuttra] were maintained across these clinically complex patient groups, as well as in patients receiving background therapies, including [Vyndamax] and disease-modifying heart failure therapies, reinforcing both the consistency of the treatment effect and its relevance in real-world clinical practice,” Solomon said.
Few issues with vitamin A found with Amvuttra use
Because the transthyretin protein helps transport vitamin A — which is key for vision — through the body, low levels of this vitamin are a well-documented side effect of Amvuttra. Patients taking Amvuttra are usually recommended to take vitamin A supplements.
In another newly presented analysis, researchers evaluated rates of adverse events related to vitamin A deficiency using pooled data from clinical trials and post-marketing safety studies on Amvuttra or its predecessor Onpattro (patisiran), also sold by Alnylam and approved to treat hATTR-PN.
The analysis covered more than 25,000 patient-years of treatment exposure; one patient-year is the equivalent of one patient being treated for one year.
These results showed that rates of potential vitamin A deficiency-related vision problems were low, and about as common in individuals taking Amvuttra or Onpattro as in those taking a placebo. Across all studies, there were no documented cases of clinically meaningful vitamin A deficiency, according to Alnylam.
“The low and comparable to placebo rates of vitamin A deficiency-related adverse events observed in this large analysis provide strong reassurance that lowering transthyretin does not meaningfully increase these events in patients with ATTR amyloidosis,” said William S. Blaner, PhD, an expert in vitamin A metabolism and transport and a professor at Columbia University.
At the congress, Alnylam also presented the design of its global observational study, called DemonsTTRate (NCT07358078), which aims to collect five-year data from an estimated 2,000 ATTR-CM patients treated in real-world clinical practice. That study is now recruiting participants at four U.S. locations.
Developer now testing next-generation therapy nucresiran
Alnylam is also developing nucresiran, a next-generation therapy that’s designed to work similarly to Amvuttra. However, this experimental therapy would be given every six months instead of every three for both ATTR-CM and hATTR-PN.
A global Phase 3 study, called TRITON-CM (NCT07052903), is now recruiting adults with ATTR-CM — at more than 200 sites worldwide — to test nucresiran against a placebo. The trial was originally designed to enroll approximately 1,250 participants, with results expected in 2030. However, because enrollment is going faster than expected, Alnylam recently announced that it is expanding the target number of participants to 1,750.
That change will provide the study more statistical power to detect meaningful effects in a shorter span of time. Nevertheless, the company still expects to commercially launch the next-generation therapy in 2030, assuming results are positive and the therapy earns regulatory approvals.
Richard Olin
Still trying to get into a study