Amvuttra approved in US to treat adults with ATTR-CM
Therapy is first gene-silencing treatment approved for condition
The U.S. Food and Drug Administration (FDA) has extended the approval of Amvuttra (vutrisiran) to adults with cardiomyopathy (heart damage) due to nonhereditary or hereditary transthyretin amyloidosis (ATTR-CM).
Alnylam Pharmaceuticals’ Amvuttra was specifically cleared for use to reduce death, hospital stays, and urgent visits due to heart problems in this patient population. With the new indication, it becomes the first and only medicine approved by the FDA to treat both familial amyloid polyneuropathy (FAP) — also known as hereditary ATTR amyloidosis with polyneuropathy — and ATTR-CM.
“The FDA approval of Amvuttra for ATTR-CM marks a pivotal advancement for patients, providing a new and clinically differentiated treatment option that has been shown to improve outcomes, including cardiovascular mortality, and reduce progression for those living with this devastating disease,” Yvonne Greenstreet, Alnylam’s CEO, said in a company press release.
Amvuttra may be covered by insurance depending on the patient’s plan. If coverage isn’t enough, patient support programs like Alnylam Assist can help.
Amvuttra’s approval “not only expands treatment options, but also represents important progress in addressing the underlying cause of ATTR-CM and improving patient outcomes,” Kristen Hsu, executive director of research at Amyloidosis Research Consortium (ARC), said in an organization press release.
ATTR amyloidosis is a group of diseases where the TTR protein, coded by the TTR gene, misfolds and forms toxic clumps, known as amyloid deposits. These toxic clumps build up in tissues, causing damage. FAP is a hereditary form of the disease marked mainly by neurological symptoms that result from damage to the nerves outside the brain and spinal cord. The disease can also affect the heart and cause cardiomyopathy, however. In ATTR-CM, which is sometimes hereditary, TTR accumulates in the heart, which, left untreated, can limit physical activity and lead to heart failure.
Treating cardiomyopathy
Already approved for adults with FAP in the U.S. and other regions, Amvuttra is a gene silencer that delivers specialized short strands of genetic material to liver cells, the main producer of transthyretin. The delivered genetic material is designed to bind to and trigger the destruction of the TTR gene’s messenger RNA, an intermediate molecule derived from DNA that guides protein production.
Without messenger RNA, the production of both healthy and mutated versions of the TTR protein is reduced and fewer amyloid deposits should form, easing symptoms of ATTR amyloidosis and slowing the disease’s progression. Amvuttra is given by injection under the skin once every three months in a hospital or clinic setting.
Its approval for ATTR-CM patients drew on positive data from HELIOS-B (NCT04153149), a Phase 3 clinical trial of 655 adults with nonhereditary or hereditary ATTR-CM. The participants were randomly assigned to Amvuttra or a placebo every three months.
Some 40% were already receiving tafamidis, an oral treatment approved in the U.S. as Vyndaqel and Vyndamax for adults with ATTR-CM. In the European Union, Vyndaqel is approved for adults in the early stages of FAP. Tafamidis works by stabilizing TTR, preventing it from misfolding and building up as amyloid deposits.
After three years, Amvuttra-treated patients had a 28% lower risk of death from any cause and recurrent cardiovascular events over those on the placebo. This risk was 33% lower among patients who weren’t on background treatment with tafamidis.
The benefits were even more pronounced with longer follow-up, including three years of the placebo-controlled part and six months of Amvuttra treatment in the trial’s open-label extension portion.
“Amvuttra is a major advancement for patients with ATTR-CM as it introduces the first gene-silencing approach to treating this disease,” Hsu said. With Amvuttra, “patients now have a choice between two distinct disease-modifying treatment strategies — TTR stabilizers or TTR gene silencers — allowing for a more personalized approach to care.”
Over three years, Amvuttra also resulted in less of a decline in physical function, as measured by the distance patients covered on a six-minute walk test, and in quality of life. Its side effects were consistent with those seen during clinical testing in adults with FAP.
Amvuttra “allowed patients to live longer, experience fewer hospitalizations, and improve how they function and feel,” said Ronald Witteles, MD, a HELIOS-B investigator and co-director of the Stanford Amyloid Center. HELIOS-B “enrolled patients who mirror the real-world population with this disease, and I am very encouraged by [Amvuttra’s] ability to demonstrate meaningful clinical benefits across both cardiovascular outcomes and multiple measures of disease progression.”
Greenstreet said Amvuttra’s approval “represents a significant milestone in our nearly [20] years of partnership with the ATTR amyloidosis community, but we are not stopping here. We will continue to innovate for patients with ATTR amyloidosis so they can live longer, better, healthier lives.”
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