FDA Approves Alnylam’s Amvuttra for ATTR-CM

Rare Daily Staff

The U.S. Food and Drug Administration expanded the approved use of Alnylam Pharmaceuticals’ RNAi therapeutic Amvuttra ATTR-CM, a rapidly progressive and fatal cardiomyopathy.

The approval covers the use of Amvuttra to treat cardiomyopathy caused by wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits.

The FDA previously approved Amvuttra for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.

ATTR-CM affects approximately 150,000 people in the United States and more than 300,000 people worldwide. The deposition of misfolded transthyretin (TTR) fibrils causes irreversible damage over time that can lead to premature death. There is no cure for ATTR-CM.

Amvuttra works upstream to deliver rapid knockdown of TTR, addressing the disease at its source, with only four convenient subcutaneous doses per year. By rapidly knocking down TTR production, Amvuttra substantially decreases deposition of TTR fibrils, which form amyloid and cause irreversible cardiovascular damage and premature death in patients with ATTR-CM.

The approval is based on the HELIOS-B phase 3 clinical trial, which evaluated Amvuttra for the treatment of ATTR-CM. The trial achieved statistical significance compared to placebo on all 10 pre-specified primary and secondary endpoints. The results were presented at the European Society of Cardiology Congress and simultaneously published in The New England Journal of Medicine.

In the overall population, Amvuttra reduced the risk of all-cause mortality and recurrent cardiovascular events by 28 percent during the double-blind treatment period of up to 36 months. Mortality in this population was significantly reduced by 36 percent through 42 months in a pre-specified secondary endpoint analysis, which included up to 36 months of the double-blind period plus six months of open-label extension. In the monotherapy population.

“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,” said Yvonne Greenstreet, CEO of Alnylam. “

“This FDA approval provides an opportunity to further transform ATTR-CM treatment with a new mechanism of action. The HELIOS-B clinical trial found that vutrisiran allowed patients to live longer, experience fewer hospitalizations, and improve how they function and feel,” said Ronald Witteles, HELIOS-B investigator, professor of medicine at Stanford University School of Medicine and co-director of the Stanford Amyloid Center. “The trial enrolled patients who mirror the real-world population with this disease, and I am very encouraged by vutrisiran’s ability to demonstrate meaningful clinical benefits across both cardiovascular outcomes and multiple measures of disease progression.”

Alnylam charges about $$476,000 a year for Amvuttra. That is considerably more than the estimated $250,000 a year that Pfizer and BridgeBio each charge for their competing oral ATTR-CM therapies.

Alnylam said in Amvuttra in hATTR-PN is covered by insurers for about 99 percent of patients with the majority paying no money out-of-pocket. It said it expects similar broad coverage and out-of-pocket costs in ATTR-CM given comparable payer dynamics and the clinical value demonstrated in the HELIOS-B clinical trial.

Photo: Yvonne Greenstreet, CEO of Alnylam