What side effects are associated with this type of intervention?

Common treatments for Hereditary Angioedema (HAE) include C1-inhibitor replacement therapy, bradykinin B2 receptor antagonists, and kallikrein inhibitors. Known side effects of these treatments can include injection site reactions, hypersensitivity reactions, and potential thromboembolic events. For antisense oligonucleotides like Donidalorsen, side effects may include injection site reactions, flu-like symptoms, and liver enzyme elevations. It is important to discuss these potential side effects with a healthcare provider to determine the best treatment plan.

What prior FDA approvals exist?

The FDA has approved several treatments for Hereditary Angioedema (HAE), including C1 esterase inhibitors (such as Berinert and Cinryze), kallikrein inhibitors (such as Ecallantide and Lanadelumab), and bradykinin receptor antagonists (such as Icatibant). These treatments aim to prevent or reduce the frequency of HAE attacks. Donidalorsen, an antisense oligonucleotide targeting prekallikrein, is being studied for its long-term safety and efficacy in reducing HAE attacks, representing a novel approach in the management of HAE.

What other types of research exist?

Promising novel alternatives to Donidalorsen for HAE patients include Lanadelumab (a monoclonal antibody targeting plasma kallikrein), Berotralstat (an oral plasma kallikrein inhibitor), and gene therapy approaches targeting the underlying genetic causes of HAE. These treatments have shown efficacy in reducing HAE attack frequency and improving patient outcomes in clinical trials.

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Monoclonal Antibodies

Donidalorsen for Hereditary Angioedema

Phase 3

Recruiting

Research Sponsored by Ionis Pharmaceuticals, Inc.

Eligibility Criteria Checklist

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

Must have

Participants must have access to, and the ability to use, ≥ 1 acute medication(s) (e.g., plasma-derived or recombinant C1-INH concentrate or a bradykinin receptor (BK) 2-receptor antagonist) to treat angioedema attacks.

Participants must have a documented diagnosis of HAE-1/HAE-2.

Must not have

Exposure to any of the following medications: Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption.

Concurrent diagnosis of any other type of recurrent angioedema, including acquired, idiopathic angioedema or HAE with normal C1-INH (also known as HAE Type III).

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 157 weeks for group 1 and group 2

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing donidalorsen, a medication for people with Hereditary Angioedema (HAE) Types I and II. The goal is to see if it can reduce the number of swelling attacks and improve quality of life. Donidalorsen works by targeting pathways in the body that cause these attacks. Donidalorsen treatment resulted in a significantly lower rate of angioedema attacks.

Who is the study for?

This trial is for individuals aged 12 or older with a confirmed diagnosis of Hereditary Angioedema (HAE) types 1 or 2. They must have completed a previous study through Week 25, be on stable HAE prophylaxis treatment, and able to manage acute attacks. Excluded are those with recent malignancies, certain medication exposures, hypersensitivity to donidalorsen, other angioedema types, drug/alcohol abuse history.

What is being tested?

The trial studies the long-term safety and effectiveness of donidalorsen in preventing HAE attacks. It aims to understand how this intervention affects the frequency of attacks and quality of life over an extended period for people living with HAE.

What are the potential side effects?

While specific side effects aren't listed here, participants will be monitored for any adverse reactions due to long-term use of donidalorsen. Potential side effects may include reactions at injection sites or allergic responses if sensitivity to the drug exists.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can access and use medication for sudden swelling attacks.

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I have been diagnosed with hereditary angioedema type 1 or 2.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have taken ACE inhibitors or estrogen medications.

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I have been diagnosed with a type of recurrent swelling not caused by HAE Type I/II.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 157 weeks for group 1 and group 2

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 157 weeks for group 1 and group 2

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 157 weeks for group 1 and group 2 for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Angioedema Quality of Life (AE-QoL) Questionnaire Total Score

Side effects data

From 2021 Phase 2 trial • 23 Patients • NCT04030598

33%

Application site rash

33%

Hyperhidrosis

33%

Vomiting

33%

Feeling hot

100%

80%

60%

40%

20%

Study treatment Arm

Part B: Donidalorsen 80 mg

Part A: Placebo

Part A: Donidalorsen 80 mg

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: OLE ParticipantsExperimental Treatment1 Intervention

Group 1 and Group 2 participants will be administered donidalorsen by SC injection for up to 157 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Donidalorsen

2021

Completed Phase 3

~150

0 / 4Eligibility criteria met

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

The most common treatments for Hereditary Angioedema (HAE) often target the bradykinin pathway, which is responsible for the swelling episodes characteristic of the condition. Donidalorsen, an antisense oligonucleotide, works by reducing the production of prekallikrein, a precursor to kallikrein. Kallikrein is an enzyme that increases the production of bradykinin, a peptide that causes blood vessels to become more permeable, leading to swelling. By lowering prekallikrein levels, Donidalorsen helps to reduce bradykinin production, thereby preventing or lessening the severity of HAE attacks. This targeted approach is significant for HAE patients as it addresses the root cause of their symptoms, potentially offering more effective and sustained relief.