What is the mechanism of action of this treatment?

Eplontersen and similar treatments for Transthyretin-Mediated Amyloid Polyneuropathy (hATTR-PN) work by reducing the production of transthyretin (TTR) protein. These treatments often use antisense oligonucleotides (ASOs) or small interfering RNA (siRNA) to target and degrade the mRNA responsible for TTR production in the liver. By lowering TTR levels, these therapies aim to reduce the formation of amyloid deposits that cause nerve damage and other symptoms in hATTR-PN patients. This mechanism is crucial as it directly addresses the root cause of the disease, potentially slowing or halting its progression and improving patients' quality of life.

What side effects are associated with this type of intervention?

The most common treatments for Transthyretin-Mediated Amyloid Polyneuropathy (hATTR-PN) that focus on reducing TTR protein production, such as Eplontersen, generally have side effects that include injection site reactions, nausea, fatigue, and elevated liver enzymes. In some cases, more severe adverse events like thrombocytopenia (low platelet count) and renal impairment have been reported. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN) that focus on reducing TTR protein production. Notably, patisiran (Onpattro) and inotersen (Tegsedi) are two such drugs. Patisiran is an RNA interference (RNAi) therapeutic that targets and degrades TTR mRNA, thereby reducing the production of the TTR protein. Inotersen is an antisense oligonucleotide that binds to TTR mRNA, leading to its degradation and subsequent reduction in TTR protein synthesis. These treatments aim to decrease the accumulation of amyloid deposits and alleviate the symptoms of hATTR-PN.

What other types of research exist?

Promising alternatives to Eplontersen for hATTR-PN patients include Patisiran and Inotersen, both of which reduce TTR protein production. Additionally, Tafamidis and AG10 are TTR stabilizers that prevent amyloid formation and have shown efficacy in clinical trials.

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Antisense Oligonucleotide

Eplontersen for Amyloid Neuropathy

Phase 3

Waitlist Available

Research Sponsored by Ionis Pharmaceuticals, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline to week 181

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing the safety of Eplontersen, a medication given regularly, in patients with a genetic condition that causes nerve damage. The treatment works by lowering harmful protein levels to reduce nerve damage.

Who is the study for?

This trial is for adults with hereditary transthyretin-mediated amyloid polyneuropathy who have completed certain previous studies. Participants must agree to vitamin A supplementation, use contraception if fertile, and be able to follow study requirements. Pregnant or breastfeeding women are excluded.

What is being tested?

The trial tests the long-term safety and effectiveness of Eplontersen in patients with hATTR-PN. It aims to understand how well patients tolerate extended dosing of this medication over a longer period.

What are the potential side effects?

While specific side effects for Eplontersen aren't listed here, similar medications may cause injection site reactions, fatigue, nausea, headache, and potential liver issues. Monitoring will occur for any adverse effects during the trial.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline to week 181

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline to week 181

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline to week 181 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Change From Baseline in 5 Level EQ-5D (EQ-5D-5L)

Change From Baseline in Composite Autonomic Symptom Score-31 (COMPASS-31)

Change From Baseline in Modified Body Mass Index (mBMI)

+5 more

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: EplontersenExperimental Treatment1 Intervention

Eplontersen will be administered by subcutaneous (SC) injection once every 4 weeks for up to 3 years (157 weeks).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AKCEA-TTR-LRx

Not yet FDA approved

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Eplontersen and similar treatments for Transthyretin-Mediated Amyloid Polyneuropathy (hATTR-PN) work by reducing the production of transthyretin (TTR) protein. These treatments often use antisense oligonucleotides (ASOs) or small interfering RNA (siRNA) to target and degrade the mRNA responsible for TTR production in the liver. By lowering TTR levels, these therapies aim to reduce the formation of amyloid deposits that cause nerve damage and other symptoms in hATTR-PN patients. This mechanism is crucial as it directly addresses the root cause of the disease, potentially slowing or halting its progression and improving patients' quality of life.

Association of Amyloid Reduction After Donanemab Treatment With Tau Pathology and Clinical Outcomes: The TRAILBLAZER-ALZ Randomized Clinical Trial.Targeting transthyretin - Mechanism-based treatment approaches and future perspectives in hereditary amyloidosis.Lessons Learnt from the Second Generation of Anti-Amyloid Monoclonal Antibodies Clinical Trials.