What is the mechanism of action of this treatment?

Antisense oligonucleotides like Donidalorsen work by targeting and degrading specific mRNA sequences to reduce the production of plasma kallikrein, a protein that plays a critical role in the generation of bradykinin. Bradykinin increases vascular permeability, leading to the swelling seen in Hereditary Angioedema (HAE) attacks. By lowering plasma kallikrein levels, these treatments can decrease bradykinin production, thereby preventing or reducing the severity of HAE attacks. This targeted approach is significant for HAE patients as it directly addresses the root cause of their symptoms, potentially offering more effective and precise management of the condition.

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, upper respiratory tract infections, headache, dizziness, and gastrointestinal symptoms such as nausea and diarrhea. For antisense oligonucleotides like Donidalorsen, potential side effects may include injection site reactions, flu-like symptoms, and possible renal toxicity, necessitating regular monitoring of kidney function.

What prior FDA approvals exist?

FDA-approved treatments for Hereditary Angioedema (HAE) include C1 esterase inhibitors (such as Berinert and Cinryze), which replace the deficient or dysfunctional protein in patients with HAE. Other treatments include kallikrein inhibitors like Ecallantide (Kalbitor) and Lanadelumab (Takhzyro), which directly inhibit plasma kallikrein to prevent bradykinin production and subsequent angioedema attacks. These treatments are similar to Donidalorsen, which targets Prekallikrein mRNA to reduce plasma kallikrein levels, thereby aiming to control HAE symptoms.

What other types of research exist?

Promising novel alternatives to Donidalorsen for Hereditary Angioedema patients include: 1) Lanadelumab, a monoclonal antibody that inhibits plasma kallikrein, which has shown efficacy in reducing HAE attacks. 2) Berotralstat, an oral plasma kallikrein inhibitor, which has been approved for prophylactic treatment of HAE. 3) Icatibant, a bradykinin B2 receptor antagonist, used for acute treatment of HAE attacks. These alternatives target similar pathways and have demonstrated effectiveness in managing HAE.

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Antisense Oligonucleotide

Donidalorsen for Hereditary Angioedema

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up week 25

Awards & highlights

Pivotal Trial

Summary

This trial is testing donidalorsen, a medication, to see if it can help people with Hereditary Angioedema (HAE) by reducing the frequency and severity of their swelling attacks. The study aims to improve their quality of life. Donidalorsen has shown a significantly lower rate of angioedema attacks in earlier tests.

Who is the study for?

This trial is for people aged 12 or older with a confirmed diagnosis of hereditary angioedema types 1 or 2, who have had at least two attacks during the screening period. They must be able to provide consent and manage their acute attack medications. Exclusions include prior participation in related studies, recent use of certain prophylactic drugs, drug/alcohol abuse, other angioedema diagnoses, significant lab abnormalities, and recent investigational drug treatment.

What is being tested?

The OASIS-HAE study is testing the safety and effectiveness of Donidalorsen compared to a placebo in individuals with Hereditary Angioedema (HAE). It aims to see how well Donidalorsen can reduce HAE attacks and improve quality of life for patients.

What are the potential side effects?

While specific side effects are not listed here, participants may experience reactions related to Donidalorsen or placebo administration. Common side effects in trials like this could include injection site reactions, flu-like symptoms, nausea, fatigue or allergic responses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ week 25

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~week 25

This trial's timeline: 3 weeks for screening, Varies for treatment, and week 25 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 in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score at Week 25

Percentage of Participants who are Well Controlled on the Angioedema Control Test (AECT) at Week 25

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

Pivotal Trial

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

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Donidalorsen: Cohort BExperimental Treatment1 Intervention

Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.

Group II: Donidalorsen: Cohort AExperimental Treatment1 Intervention

Participants will be administered donidalorsen by subcutaneous (SC) injection for up to 25 weeks.

Group III: Placebo: Cohort APlacebo Group1 Intervention

Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.

Group IV: Placebo: Cohort BPlacebo Group1 Intervention

Participants will be administered donidalorsen-matching placebo by subcutaneous (SC) injection for up to 25 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Donidalorsen

2021

Completed Phase 3

~150

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

Antisense oligonucleotides like Donidalorsen work by targeting and degrading specific mRNA sequences to reduce the production of plasma kallikrein, a protein that plays a critical role in the generation of bradykinin. Bradykinin increases vascular permeability, leading to the swelling seen in Hereditary Angioedema (HAE) attacks. By lowering plasma kallikrein levels, these treatments can decrease bradykinin production, thereby preventing or reducing the severity of HAE attacks. This targeted approach is significant for HAE patients as it directly addresses the root cause of their symptoms, potentially offering more effective and precise management of the condition.

Targeting TGFβ Signaling to Address Fibrosis Using Antisense Oligonucleotides.Dual suppression of hemangiogenesis and lymphangiogenesis by splice-shifting morpholinos targeting vascular endothelial growth factor receptor 2 (KDR).AT1 receptor mRNA antisense normalizes enhanced cardiac sympathetic afferent reflex in rats with chronic heart failure.