Vutrisiran (ALN-TTRsc02)

Vutrisiran (previously ALN-TTRsc02) is a treatment that Alnylam Pharmaceuticals is developing for familial amyloid polyneuropathy, or FAP, and other types of ATTR amyloidosis.

How does vutrisiran work?

FAP is a condition characterized by the buildup of abnormal deposits of proteins, or amyloids, in different organs and tissues.

It is caused by mutations of the TTR gene, which provides the instructions necessary to produce a protein called transthyretin. Transthyretin transports vitamin A and a hormone called thyroxine throughout the body.

Vutrisiran targets faulty mRNA, the intermediate messenger molecule between the TTR gene and transthyretin protein. By binding to TTR mRNA, vutrisiran triggers a natural process called RNA interference that promotes the destruction of mRNA. RNA interference prevents the production of the faulty transthyretin protein that causes the disease.

Vutrisiran in clinical trials

A Phase 1 study (NCT02797847) investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of increasing doses of vutrisiran in healthy volunteers. Pharmacokinetics refers to the body’s effect on a drug, while pharmacodynamics refers to a drug’s effect on the body.

Researchers looked at whether vutrisiran triggered changes in participants’ health. They also studied any impact the drug had on the body by assessing levels of transthyretin protein and vitamin A in the blood. Safety measurements included vital signs, physical examinations, laboratory evaluations, electrocardiograms, and adverse events monitoring.

Preliminary data showed that the 48 participants tolerated vutrisiran well. Patients experienced no serious adverse events, and none had to discontinue the treatment due to side effects. Adverse events were mild or moderate. They included redness and pain at the injection site, itching, cough, nausea, fatigue, and abdominal pain.

A single 25-mg dose of vutrisiran reduced the production of transthyretin protein by up to 98.4 percent for more than four months, while a 50-mg dose reduced it by 86.2 percent.

Additional preliminary data in 80 participants showed 5 to 300 mg doses of vutrisiran were well tolerated with no serious adverse events reported. The results also showed a reduction in the TTR protein which lasted for an extended period of time. The Phase 1 trial concluded in January 2018.

Vutrisiran is also being investigated in two Phase 3 clinical trials. The first, nicknamed HELIOS-A (NCT03759379), is investigating vutrisiran in patients with hereditary transthyretin amyloidosis (hATTR) also known as familial amyloid polyneuropathy (FAP). The trial has enrolled the 160 participants it was targeting. Participants will receive either 25 mg subcutaneous injections of vutrisiran once every 12 weeks or intravenous injections of Onpattro once every three weeks. Patients will be evaluated at 6 and 18th months using various functional task measurements. The trial is estimated to conclude in May 2024.

The second Phase 3 trial is called HELIOS-B (NCT04153149) and is investigating vutrisiran in patients with transytheretin amyloidosis but also cardiomyopathy (heart disease). Participants will receive either 25 mg subcutaneous injections of vutrisiran every 3 weeks or a placebo. The number of cardiovascular-related hospitalizations, as well as scores on several functional assessments, will be monitored for participants for up to 36 months. The trial is still recruiting participants and is expected to be complete by June 2025.

Other information

Vutrisiran has been granted orphan drug designation by both the US Food and Drug Administration (FDA) and European Union (EU).


Last updated: Mar. 13, 2020


FAP News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.