Vutrisiran, With the FDA’s Sign-off, Joins the Fray for ATTR-CM

Vutrisiran (Amvuttra), a small-interfering RNA (siRNA) therapy, is now the third drug approved by the US Food and Drug Administration for the treatment of adults with transthyretin amyloid cardiomyopathy (ATTR-CM), manufacturer Alnylam announced Thursday.

Approximately 150,000 people in the United States and more than 300,000 people worldwide have ATTR-CM, which results from ATTR amyloidosis. Vutrisiran had already, in 2022, received FDA approval for the treatment of hereditary transthyretin amyloid polyneuropathy (hATTR-PN).

The agency’s decision to expand the indication to individuals with either wild-type or hereditary ATTR-CM was based on the HELIOS-B randomized trial of 655 patients, with the study showing that subcutaneous treatment with vutrisiran every 3 months lowered the risk of all-cause mortality and recurrent cardiovascular events by 28% compared with placebo. The subset of patients not on background tafamidis saw an even greater 33% reduction in that endpoint.

“This is a really exciting day for the field of ATTR amyloidosis, and for all of the patients confronting the disease,” Ronald Witteles, MD (Stanford University School of Medicine, CA), wrote in an email to TCTMD. “It’s incredible to think of how far we have come in such a short time—from not a single approved therapy 6 years ago, to a world where we have three approved therapies for ATTR amyloid cardiomyopathy, along with four approved therapies for ATTR amyloid polyneuropathy. It’s truly extraordinary.”

For ATTR-CM, the available drugs work via two distinct mechanisms of action and have different modes/frequences of administration, thus giving patients and clinicians multiple options—with strong treatment effects—to choose from, he added. “For those of us who have been in the field when the best we could do was ‘supportive care,’ you almost have to pinch yourself to believe it’s real.”

The Price Tag

The drug now enters what’s becoming a crowded market for treating ATTR-CM, joining acoramidis (Attruby; BridgeBio), approved in November 2024, and tafamidis (Vyndaqel and Vyndamax; Pfizer), approved in May 2019. When tafamidis was first approved, its list price of $268,000 per year drew condemnation.

An Alnylam spokesperson told TCTMD that the company’s list price per prefilled syringe of vutrisiran will be $119,351, or $477,404 a year—the current cost of the drug when used for hATTR-PN. However, 99% of patients taking vutrisiran for hATTR-PN “are covered with the majority paying $0 out of pocket, and we expect similar broad coverage in ATTR-CM,” she specified, adding that the company offers various financial assistance and support programs for patients.

Rodney Falk, MD (Brigham and Women’s Hospital, Boston, MA), like Witteles, noted that vutrisiran has a mechanism that’s unique among the currently approved drugs. It works by inhibiting the production of hepatic transthyretin, whereas tafamidis and acoramidis stabilize transthyretin by binding to its tetramer, thus reducing its breakdown. Vutrisiran is given via subcutaneous injection four times per year, and the others are taken orally (tafamidis once daily and acoramidis twice daily).

The newer drug’s price, while higher than its predecessors, isn’t unexpected, he commented to TCTMD.

Notably, though, vutrisiran injections must be given in a medical setting and fall under Medicare Part B, so have no copay, said Falk. “So it actually is cheaper for some patients.” Tafamidis and acoramidis, taken orally, are covered under Medicare Part D.

On the horizon is eplontersen (Ionis Pharmaceuticals), an siRNA that’s injected monthly and now under study in the CARDIO-TTRansform trial, he noted, predicting that in 18 months this drug, too, will be available for ATTR-CM patients.