Vutrisiran Approved by FDA to Treat FAP Under Brand Name Amvuttra
Vutrisiran — now known by the brand name Amvuttra — has been approved by the U.S. Food and Drug Administration (FDA) to treat familial amyloid polyneuropathy (FAP), also known as hereditary transthyretin-mediated (hATTR) amyloidosis with polyneuropathy.
The therapy is expected to be available for shipment to healthcare providers in the U.S. by early July, according to its developer, Alnylam Pharmaceuticals.
Alnylam has set the list price for Amvuttra at $463,500 per year. A program called Alnylam Assist is available to help patients prescribed the medication to gain access to it.
“Today we celebrate the FDA’s approval of vutrisiran, a welcomed treatment option for hATTR amyloidosis patients experiencing the challenges of the polyneuropathy of the disease,” Isabelle Lousada, founder and CEO of the Amyloidosis Research Consortium, said in a press release.
“With this approval, Alnylam has expanded treatment options that may support improvements in quality of life, providing hope for patients and families in the amyloidosis community,” Lousada said.
In a Phase 3 study that led to the therapy’s approval, more than 50% of patients saw their disease symptoms halted or reversed.
“Amvuttra has the potential to change the standard of care for people living with the polyneuropathy of this devastating disease,” said Yvonne Greenstreet, Alnylam’s CEO, adding, “We are so thankful to the patients, families and investigators involved in making Amvuttra a reality for the hATTR amyloidosis community.”
An inherited disease, FAP is caused by mutations in the TTR gene, which provides instructions for making a protein called transthyretin. FAP-causing mutations result in the production of an abnormal form of this protein, which tends to form clumps, called amyloid fibrils, that build up in the body’s tissues, especially the nerves and heart.
When the TTR gene is used to produce transthyretin, the genetic code is copied from the cell’s DNA into a temporary molecule called messenger RNA (mRNA). That is then shuttled to the cell’s protein-making machines, called ribosomes.
Amvuttra is designed to reduce the production of transthyretin protein by binding and destroying TTR mRNA. This mechanism is virtually identical to that of Onpattro (patisiran), an FDA-approved treatment for FAP also developed by Alnylam.
The new therapy was created to have greater stability in the body than Onpattro, potentially leading to a longer and more potent therapeutic effect.
“Twenty years ago, Alnylam was founded with the bold vision for RNA interference to make a meaningful impact on the lives of people around the world in need of new approaches to address serious diseases with significant unmet medical needs, such as hATTR amyloidosis,” Greenstreet said.
“As the fifth RNAi therapeutic developed by Alnylam to receive regulatory approval in less than four years, we believe Amvutra represents an important milestone that brings us one step closer to achieving our … goals aimed at Alnylam’s transition to a leading biotech company,” she added.
Alnylam’s application to the FDA was supported by data from the Phase 3 HELIOS-A trial (NCT03759379). That study enrolled 164 people with FAP, who were assigned to treatment with Amvuttra — given by an under-the-skin (subcutaneous) injection every three months — or Onpattro, administered via an infusion directly into the bloodstream every three weeks.
While the trial is ongoing, Alnylam reported 18-month data from the study earlier this year. Results showed that treatment with Amvuttra led to a 0.46-point mean decrease (improvement) in the modified Neuropathy Impairment Score (mNIS+7), an assessment of neuropathy symptom severity. By comparison, among FAP patients given a placebo in an earlier clinical trial, mNIS+7 scores worsened by more than 28 points in the same time period.
Treatment with Amvuttra in HELIOS-A also led to improvements in walking speed, nutritional status, overall disability status, and quality of life. Transthyretin levels also were reduced by a mean of 88%. Exploratory data from the study, recently announced by Alnylam, also suggested Amvuttra was able to reduce heart damage in patients with cardiac involvement.
The most common side effects reported in patients given Amvuttra included joint pain, shortness of breath, and decreased vitamin A levels. Five patients experienced injection site reactions, all of which were mild and temporary.
“Amvuttra is a new therapeutic option that has demonstrated the potential to halt or reverse polyneuropathy progression in patients with an acceptable safety profile, along with an infrequent, subcutaneous dosing regimen that may also help to improve the disease management experience for patients,” said Michael Polydefkis, MD, a professor at Johns Hopkins Neurology and an investigator in HELIOS-A.
“The FDA approval of Amvuttra is very encouraging for the hATTR amyloidosis community, who need additional therapies to address the polyneuropathy of this progressive, life-threatening, multisystem disease,” Polydefkis added.
Amvuttra also is being considered for approvals in Brazil, Japan, and the EU.
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