Vutrisiran for Transthyretin Amyloidosis with Cardiomyopathy

Not currently recruiting at 107 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alnylam Pharmaceuticals

Disqualifiers: Primary amyloidosis, NYHA Class IV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called vutrisiran to determine its effectiveness for people with transthyretin amyloidosis and heart problems (cardiomyopathy). The goal is to assess the safety and effectiveness of vutrisiran when administered as an injection every three months. Participants will receive either vutrisiran or a placebo. This trial suits those diagnosed with transthyretin amyloidosis and heart issues who have experienced heart failure symptoms, such as hospital visits for heart problems. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that vutrisiran is likely to be safe for humans?

Research has shown that vutrisiran is generally safe for individuals with transthyretin amyloidosis and heart problems. Studies found that participants taking vutrisiran experienced fewer stomach and digestion issues than those not taking it. Additionally, those on vutrisiran had a lower risk of death from any cause and experienced fewer heart problems compared to those on a placebo. Overall, evidence suggests that vutrisiran is relatively safe, with fewer serious side effects than no treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for amyloidosis?

Vutrisiran is unique because it offers a new approach for treating transthyretin amyloidosis with cardiomyopathy by silencing the transthyretin (TTR) gene, effectively reducing the production of the abnormal protein that causes the disease. Unlike existing treatments such as tafamidis or diflunisal, which primarily stabilize the TTR protein, vutrisiran targets the root of the problem by decreasing the production of the protein itself. Additionally, it is administered via a convenient subcutaneous injection once every three months, which could improve patient adherence and quality of life compared to more frequent dosing schedules. Researchers are excited about its potential not only for its novel mechanism of action but also for its promising efficacy and ease of use.

What evidence suggests that vutrisiran might be an effective treatment for cardiomyopathy?

Studies have shown that vutrisiran effectively treats transthyretin amyloidosis with cardiomyopathy (ATTR-CM). In this trial, participants will receive either vutrisiran or a placebo. Research indicates that patients taking vutrisiran have a lower risk of dying from any cause and experience fewer heart-related problems compared to those on a placebo. Specifically, vutrisiran reduces heart issues, such as hospital visits for heart failure, and deaths related to heart problems. Additionally, evidence shows that vutrisiran improves overall heart function in patients with ATTR-CM. Overall, the data supports that vutrisiran can significantly benefit those with this condition. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Alnylam Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with a confirmed diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, which includes inherited or wild-type forms. Participants should have a history of heart failure, evidenced by hospitalization or clinical signs. Those with primary or leptomeningeal amyloidosis, severe polyneuropathy, advanced heart failure, very low kidney function, prior TTR treatments, or other types of cardiomyopathies cannot join.

Inclusion Criteria

I have been hospitalized for heart failure before or show signs of it.

I have been diagnosed with a type of heart disease caused by transthyretin amyloidosis.

Exclusion Criteria

I have been diagnosed with primary or leptomeningeal amyloidosis.

I have a heart condition not caused by TTR amyloidosis.

I have severe nerve damage affecting my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive vutrisiran 25 mg SC or placebo once every 3 months

Up to 36 months

Visits every 3 months

Randomized Treatment Extension (RTE)

Participants receive vutrisiran 25 mg SC every 3 months or 50 mg SC every 6 months

Duration not specified

Open-label Extension (OLE)

Participants receive vutrisiran 25 mg SC every 3 months

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vutrisiran

Trial Overview The study tests the effectiveness and safety of Vutrisiran given as an injection under the skin every three months compared to a placebo (saline solution). The goal is to see if Vutrisiran can help patients with ATTR amyloidosis affecting the heart.

How Is the Trial Designed?

Group I: Vutrisiran 25 mg Experimental Treatment 1 Intervention

Participants received vutrisiran 25 milligrams (mg) administered subcutaneously (SC) once every 3 months (q3M) during the 36-month double-blind (DB) period. After the DB period, participants continue receiving vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the open-label treatment extension (OLE) period.

Group II: Placebo Placebo Group 2 Interventions

Participants received vutrisiran matching placebo administered SC q3M during the 36-month DB period. After the DB period, participants receive vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the OLE period.

Who Is Running the Clinical Trial?

Alnylam Pharmaceuticals

Lead Sponsor

Trials

81

Recruited

16,100+

Dr. Yvonne Greenstreet

Alnylam Pharmaceuticals

Chief Executive Officer since 2021

MD from the University of Leeds, MBA from INSEAD

Dr. Pushkal Garg

Alnylam Pharmaceuticals

Chief Medical Officer since 2016

MD from Columbia University

Published Research Related to This Trial

Vutrisiran, an RNA interference therapy targeting the TTR gene, has been shown to significantly reduce neuropathy impairment in patients with hereditary transthyretin-mediated amyloidosis, based on a pivotal phase 3 study.

The treatment is generally well tolerated, with the main side effects being pain in extremities and arthralgia, and it offers the convenience of subcutaneous administration every three months, making it a practical option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis. Nie, T., Heo, YA., Shirley, M.[2023]

A 78-year-old woman with hereditary transthyretin cardiac amyloidosis showed improvement after six months of treatment with patisiran, as indicated by decreased levels of N-terminal pro B-type natriuretic peptide and left ventricular mass index.

Patisiran appears to be a promising disease-modifying treatment for advanced hereditary transthyretin cardiac amyloidosis, but more research with larger groups of patients is needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patisiran for advanced heart failure with hereditary transthyretin cardiac amyloidosis. Nakamura, M., Imamura, T., Kinugawa, K.[2021]

Citations

1. jacc.org jacc.org/doi/10.1016/j.jacc.2025.04.008

Vutrisiran Improves Survival and Reduces Cardiovascular ... Vutrisiran reliably reduced the risk of ACM, CV mortality, CV hospitalizations, HF hospitalizations, and urgent HF visits vs placebo in patients with ATTR-CM.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39213194/

Vutrisiran in Patients with Transthyretin Amyloidosis ... Among patients with ATTR-CM, treatment with vutrisiran led to a lower risk of death from any cause and cardiovascular events than placebo ...

3. nature.com nature.com/articles/s41591-025-03851-z

Effects of vutrisiran on cardiac structure and function in ... In HELIOS-B, vutrisiran significantly decreased rates of cardiovascular events and all-cause death among patients with ATTR-CM compared with ...

4. investors.alnylam.com investors.alnylam.com/press-release?id=29316

New Data from HELIOS-B Phase 3 Study Demonstrate Lower ... In the analysis, a 42% lower rate of GI events was observed in patients treated with vutrisiran in the overall population, compared to placebo.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0735109725058231

Impact of Heart Failure Severity on Vutrisiran Efficacy in ... Vutrisiran reduced the risk of all-cause mortality (ACM) and recurrent cardiovascular (CV) events in patients with transthyretin amyloidosis with ...

6. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.102066

Vutrisiran in Transthyretin Amyloidosis: A Pooled Safety ... Patients with hereditary transthyretin amyloidosis cardiomyopathy (ATTRv-CM) or ATTRwt have a median survival time after diagnosis of 2.6 to 4. ...

7. nejm.org nejm.org/doi/10.1056/NEJMoa2409134

Vutrisiran in Patients with Transthyretin Amyloidosis ... Among patients with ATTR-CM, treatment with vutrisiran led to a lower risk of death from any cause and cardiovascular events than placebo and ...