NEW YORK – The US Food and Drug Administration has approved Alnylam Pharmaceuticals' RNAi drug Amvuttra (vutrisiran) as a treatment for transthyretin amyloidosis with cardiomyopathy (ATTR-CM), the company said Thursday.
The FDA approved the company's supplemental new drug application for Amvuttra, which is already approved for TTR amyloidosis with polyneuropathy (ATTR-PN). This makes Amvuttra the only drug commercially available in the US to address both manifestations of the disease, though other drugs are in clinical development for ATTR-PN and ATTR-CM.
ATTR-PN is always hereditary, caused by mutations in the TTR gene, while ATTR-CM has a hereditary and wild-type form. In the latter form of the disease, patients have a TTR gene that produces proteins that are initially normal but become unstable and misfold later in life. In both cases, abnormal TTR proteins misfold and accumulate in the heart, forming amyloid plaques. Amvuttra, which is administered quarterly, is designed to address that issue through rapid knockdown of TTR protein production.
The FDA expanded the indication for the drug based on data from the Phase III HELIOS-B trial, in which patients with ATTR-CM received either regular subcutaneous injections of Amvuttra or placebo. Investigators observed that Amvuttra reduced the risk of all-cause mortality and recurrent cardiovascular events by 28 percent during the three-year treatment period. In a prespecified secondary endpoint analysis, mortality in the Amvuttra-treated population was significantly reduced by 36 percent over 42 months.
Researchers identified no new safety concerns in the HELIOS-B study compared to the HELIOS-A study that had underpinned the drug's approval in ATTR-PN. The most common adverse reactions that patients had experienced in the HELIOS-A study were pain in their extremities, arthralgia, dyspnea, and decreases in vitamin A, according to Alnylam.
Amvuttra has been covered by insurance for 99 percent of patients with ATTR-PN, and most don't have any out-of-pocket costs, the company said, adding that it expects the same will be true for the ATTR-CM population. The firm added that its Alnylam Assist program helps patients with insurance coverage and provides financial assistance, among other services.
Cambridge, Massachusetts-based Alnylam said marketing authorization applications for Amvuttra in ATTR-CM are also under review in Europe, Brazil, and Japan.