Alnylam’s RNAi therapeutic Amvuttra (vutrisiran) received another approval from the FDA. The drug was approved for treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality, cardiovascular hospitalizations, and urgent heart failure visits.
The world market for ATTR-CM treatments is expected to surpass $10 billion by 2030.
The approval expands the indication for Amvuttra, which now becomes the first and only therapeutic approved by the FDA for the treatment of ATTR-CM and the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults.
ATTR-CM is a devastating, rapidly progressive, and ultimately fatal disease estimated to affect approximately 150,000 people in the United States and over 300,000 people worldwide. There is no cure for ATTR-CM, and the deposition of misfolded transthyretin (TTR) fibrils can lead to premature death. Today, most patients remain undiagnosed and untreated.
“The FDA approval of Amvuttrafor 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, MBChB, CEO of Alnylam.
Amvuttra works upstream to deliver rapid knockdown of TTR, addressing the disease at its source, via four subcutaneous doses per year. By rapidly knocking down TTR production, Amvuttra substantially decreases the deposition of TTR fibrils, which form amyloid and cause irreversible cardiovascular damage and premature death.
“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, MD, 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. This is a very exciting day for patients with this challenging disease.”
This approval is based on the HELIOS-B Phase lll clinical trial, which achieved statistical significance compared to placebo on all 10 pre-specified primary and secondary endpoints.
The results of that trial 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% during the double-blind treatment period of up to 36 months.
“Despite recent advances, there remains a significant need for patients living with ATTR-CM and I’ve witnessed, firsthand, the impact that ATTR amyloidosis can have on families, including diminished quality of life and the loss of loved ones,” said Muriel Finkel, president of the Amyloidosis Support Groups. “The availability of this groundbreaking treatment option is a significant moment for patients living with ATTR amyloidosis. It represents a beacon of hope for our community.”
