Vutrisiran vs Patisiran for Amyloidosis

Not currently recruiting at 63 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Alnylam Pharmaceuticals

Disqualifiers: Liver transplant, Other amyloidosis, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Duration: 18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for hereditary transthyretin amyloidosis (hATTR amyloidosis), a condition characterized by the buildup of abnormal proteins in the body. Participants will receive either vutrisiran (ALN-TTRSC02), a new medication administered as an injection every few months, or an existing treatment called patisiran. The trial aims to compare the effectiveness and safety of vutrisiran to patisiran. Individuals diagnosed with hATTR amyloidosis who experience symptoms such as nerve damage or movement difficulties may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have received prior TTR-lowering treatment, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that vutrisiran is generally safe for patients with hereditary transthyretin amyloidosis (hATTR amyloidosis). Studies found that patients who took vutrisiran for up to 58 months experienced acceptable safety results. Common side effects were mild, such as reactions at the injection site.

For patisiran, research indicates it is also safe over long periods. Patients who used patisiran for up to five years experienced manageable side effects, including mild reactions related to the infusion.

Both treatments have undergone thorough testing, and the safety data does not reveal major concerns. However, discussing any worries with a healthcare provider before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Vutrisiran is unique because it simplifies the treatment process for amyloidosis by using a subcutaneous injection rather than the more common intravenous delivery. This approach allows for less frequent dosing, with options for either once every three months or once every six months, offering greater convenience compared to other treatments like patisiran, which requires an infusion every three weeks. Researchers are excited about vutrisiran because it targets the same protein involved in amyloidosis but with a potentially more patient-friendly administration, which could lead to better adherence and overall outcomes.

What evidence suggests that this trial's treatments could be effective for amyloidosis?

Research has shown that vutrisiran, one of the treatments in this trial, reduces the risk of death and heart problems in people with transthyretin amyloidosis (ATTR). It also maintains physical abilities and quality of life better than a placebo. Patisiran, another treatment option in this trial, has demonstrated positive results for hereditary amyloidosis, with patients experiencing better health and survival rates than those taking a placebo. In long-term studies, patisiran slowed disease progression and extended patient survival. Both treatments offer promising options for managing amyloidosis, with evidence supporting their effectiveness in improving patient outcomes. ^{1 2 3 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 adults aged 18-85 with hereditary transthyretin amyloidosis, a condition where abnormal proteins build up in the body. Participants should have specific levels of neurologic impairment and physical functioning, and not have received other TTR-lowering treatments or had a liver transplant.

Inclusion Criteria

I am mostly able to care for myself.

I have hATTR amyloidosis with a TTR mutation.

My nerve function score is within acceptable limits.

Exclusion Criteria

You have important liver function test abnormalities.

My heart condition significantly limits my physical activity.

I have received treatment to lower TTR levels before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vutrisiran SC injection every 3 months or patisiran IV injection every 3 weeks during the 18-month Treatment Period

18 months

Every 3 months (SC) or every 3 weeks (IV)

Randomized Treatment Extension (RTE)

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

Ongoing

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Patisiran
• Vutrisiran
• Vutrisiran (ALN-TTRSC02)

Trial Overview The study compares Vutrisiran, given as an injection under the skin every three months, to Patisiran, administered intravenously every three weeks. After 18 months, participants may receive Vutrisiran less frequently in an extension period.

How Is the Trial Designed?

Group I: Vutrisiran + Vutrisiran (HELIOS-A) Experimental Treatment 1 Intervention

Participants will receive vutrisiran 25 mg subcutaneous (SC) injection once every 3 months (q3M) for 18 months during the Treatment Period followed by vutrisiran 50 mg SC injection once every 6 months (q6M) or vutrisiran 25 mg q3M during the Randomized Treatment Extension (RTE) Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.

Group II: Patisiran + Vutrisiran (HELIOS-A) Active Control 2 Interventions

Participants will receive patisiran 0.3 mg/kg intravenous (IV) infusion once every 3 weeks (q3w) for 18 months during the Treatment Period followed by vutrisiran 50 mg SC injection once q6M or vutrisiran 25 mg q3M during the RTE Period. Upon implementation of Amendment 6, participants receiving vutrisiran SC 50 mg q6M will transition to vutrisiran SC 25 mg q3M at their next scheduled dosing.

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

Citations

1. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/2828606

Five-Year Results With Patisiran for Hereditary ... Patients who received patisiran in their parent study had better outcomes and survival than those receiving placebo.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11894486/

A Randomized Clinical Trial With Open-Label Extension Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2300757

Patisiran Treatment in Patients with Transthyretin Cardiac ... Patisiran is currently under investigation for the treatment of ATTR cardiac amyloidosis. Here, we present the primary efficacy and safety data ...

4. jwatch.org jwatch.org/na58817/2025/08/01/long-term-results-with-patisiran-familial-amyloidosis-with

Long-Term Results with Patisiran in Familial Amyloidosis ... In a 5-year extension study, patisiran was associated with continued attenuation of disease progression, and with improved survival when ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39804640/

A Randomized Clinical Trial With Open-Label Extension This study presents the longest-term data to date on patisiran for hATTR-PN. Objective: To present the long-term efficacy and safety of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33212063/

Long-term safety and efficacy of patisiran for hereditary ... We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with ...

7. arci.org arci.org/patisiran-attr-cm-crl/

FDA Denies Patisiran for Cardiomyopathy of ATTR ... “The data from the APOLLO-B study demonstrate the safety of ONPATTRO in patients with ATTR cardiac amyloidosis,” says Ahmad Masri, M.D. ...