Nucresiran for ATTR-CM
Fact-checked by What is nucresiran for ATTR-CM?
Nucresiran (formerly known as ALN-TTRSC04) is an experimental gene-silencing therapy being tested as a possible treatment for transthyretin amyloid cardiomyopathy (ATTR-CM).
ATTR-CM occurs when the transthyretin protein becomes unstable and forms clumps called amyloid deposits in the heart, leading to heart disease. This can develop with age (wild-type ATTR-CM) or due to mutations in the TTR gene, which contains the template to produce transthyretin (hereditary ATTR-CM).
Like other gene silencers, nucresiran aims to reduce transthyretin production, slowing or preventing its eventual buildup into amyloid deposits. The therapy contains a genetic fragment called a small interfering RNA, which binds to a TTR template molecule needed to manufacture transthyretin and promotes its destruction. With less of this template, cells make less transthyretin.
The medication, given via subcutaneous, or under-the-skin, injections, is being developed by Alnylam Pharmaceuticals, which also markets the approved gene silencing therapy Amvuttra (vutrisiran). Nucresiran is designed to be dosed less frequently than Amvuttra — twice versus four times per year — potentially offering a more convenient treatment option for patients.
Alnylam also believes nucresiran may have the potential to be used both alone and in combination with TTR stabilizers, a class of approved ATTR-CM therapies with a different mechanism.
Nucresiran is now in Phase 3 testing for ATTR-CM and hereditary transthyretin amyloidosis with polyneuropathy (ATTR-PN), a related disease in which amyloid deposits primarily affect nerves. Should the trial results be positive, Alnylam is expecting a potential commercial launch of nucresiran for ATTR-CM in 2030.
Therapy snapshot
| Treatment name | Nucresiran |
| Administration | Subcutaneous injection |
| Clinical testing | In Phase 3 clinical testing for ATTR-CM |
How will nucresiran be administered in ATTR-CM?
In a Phase 3 clinical trial, people with ATTR-CM are receiving nucresiran as a subcutaneous injection (300 mg) once every six months.
Nucresiran in ATTR-CM clinical trials
A Phase 3 trial called TRITON-CM (NCT07052903) is testing nucresiran in adults with hereditary or wild-type ATTR-CM. Altogether, it is enrolling about 1,250 participants who will be randomly assigned to receive subcutaneous injections of nucresiran (300 mg) or a placebo every six months for at least two years and up to five years.
The main goal is to measure the medication’s effects on a combined outcome of death and heart‑related hospitalizations or urgent visits. A measure of heart-related quality of life will also be assessed. After the main treatment period, all participants will be eligible to receive nucresiran every six months for up to two years. Top-line data are expected in 2030.
In a previous Phase 1 clinical trial (NCT05661916) involving healthy volunteers, a single dose of nucresiran led to substantial and sustained reductions in transthyretin levels, particularly at the dose now being tested in the Phase 3 study.
Nucresiran side effects
Side effects of nucresiran in people with ATTR-CM have not yet been reported. In healthy volunteers, the most common potential side effects included:
- upper respiratory tract infection
- headache
- stomach flu
Most of these events were mild, and no participants reported reactions at the injection site or raised other major safety concerns.
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