What side effects are associated with this type of intervention?

Common treatments for Hereditary Angioedema (HAE) include C1 Esterase Inhibitor (C1-INH) replacement therapies, bradykinin receptor antagonists, and kallikrein inhibitors. Side effects of C1-INH replacement therapies can include injection site reactions, hypersensitivity reactions, and thromboembolic events. Bradykinin receptor antagonists may cause nausea, dizziness, and injection site reactions. Kallikrein inhibitors can lead to headache, nausea, and hypersensitivity reactions. For gene therapy treatments like BMN 331, potential side effects could include immune responses to the viral vector, liver enzyme elevations, and other infusion-related reactions.

What prior FDA approvals exist?

The FDA has approved several treatments for Hereditary Angioedema (HAE), primarily focusing on C1 Esterase Inhibitor (C1-INH) replacement therapies. These include plasma-derived C1-INH products like Berinert and Cinryze, and recombinant C1-INH such as Ruconest. Additionally, newer treatments like lanadelumab (Takhzyro) and ecallantide (Kalbitor) target the kallikrein-kinin pathway to prevent HAE attacks. While these treatments manage symptoms and prevent attacks, BMN 331 represents a novel approach as a gene therapy vector designed to provide a long-term solution by expressing wild-type human C1-INH, potentially reducing the need for frequent administration of C1-INH products.

What other types of research exist?

As of 2024, promising novel alternatives to BMN 331 for Hereditary Angioedema (HAE) patients may include other gene therapies targeting C1 Esterase Inhibitor deficiency, novel biologics such as monoclonal antibodies that inhibit kallikrein or bradykinin pathways, and advanced small molecule drugs designed to stabilize C1-INH function or reduce bradykinin production. Specific examples would depend on the latest clinical trial results and approvals.

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Gene Therapy Vector

Gene Therapy for Hereditary Angioedema (HAErmony-1 Trial)

Phase 1 & 2

Waitlist Available

Research Sponsored by BioMarin Pharmaceutical

Eligibility Criteria Checklist

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

Must have

Part A only: Confirmed diagnosis of Type I HAE due to C1-INH deficiency confirmed by genotyping of the SERPING1 gene. Part B only: Confirmed diagnosis of Type I or II HAE due to C1-INH deficiency confirmed by genotyping of the SERPING1 gene

Be older than 18 years old

Must not have

Contraindication to using glucocorticosteroids (GCS), including a diagnosis of glaucoma or untreated osteoporosis

Prior gene therapy treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests BMN 331, a gene therapy given through an IV, for people with hereditary angioedema (HAE) who lack a specific protein. The therapy uses a virus to deliver a healthy gene to liver cells, enabling them to produce the missing protein. The study aims to see if this treatment is safe and effective over several years. BMN 331 is a gene therapy that uses a virus to deliver a healthy gene to liver cells, a method that has shown promise in treating various genetic disorders.

Who is the study for?

Adults diagnosed with Hereditary Angioedema (HAE) due to C1-INH deficiency, who are on a stable HAE medication regimen or have had frequent attacks. Participants must be able to manage acute attacks at home, avoid alcohol for 52 weeks post-treatment, and use effective contraception. Excluded are those with recent high-dose androgen use, active infections including COVID-19, certain medical conditions like untreated osteoporosis or significant liver disease, prior gene therapy treatment, or risk of thrombosis.

What is being tested?

The trial is testing BMN 331 gene therapy as a potential treatment for HAE. It involves different doses of the drug given through an IV infusion using an AAV5 virus vector designed to express normal human C1 Esterase Inhibitor in the liver. This Phase 1/2 study will gradually increase doses (dose-escalation) and then expand the number of participants at selected dose levels (dose-expansion).

What are the potential side effects?

Potential side effects may include reactions related to immune response against the viral vector or infused protein such as fatigue, headache, muscle pain; possible liver inflammation; increased risk of blood clots; and complications from long-term glucocorticosteroid use if required.

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

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I cannot use steroids due to glaucoma or untreated osteoporosis.

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I have received gene therapy before.

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I have a serious health condition besides skin cancer that needs regular treatment.

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I have a history or risk of serious blood clots.

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I do not have any active infections or conditions that weaken my immune system.

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I have a significant liver condition, like NASH, hepatitis B or C, or autoimmune hepatitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 5 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Number of participants with treatment-emergent adverse events following a single IV administration of BMN 331

Awards & Highlights

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: BMN 331Experimental Treatment7 Interventions

AAV Gene Therapy Infusion

0 / 7Eligibility 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

Hereditary Angioedema (HAE) is primarily treated by addressing the deficiency or dysfunction of C1 Esterase Inhibitor (C1-INH), a protein that regulates various pathways in the immune system. Common treatments include C1-INH replacement therapies, which provide the missing or dysfunctional protein, and newer gene therapy approaches like BMN 331. BMN 331 uses an adeno-associated virus (AAV5) vector to deliver a functional copy of the C1-INH gene to the patient's liver cells, enabling them to produce the necessary protein. This gene therapy aims to provide a long-term solution by correcting the underlying genetic defect, potentially reducing the frequency and severity of HAE attacks. These treatments are crucial for HAE patients as they help manage symptoms, prevent life-threatening swelling episodes, and improve overall quality of life.