Enrollment Opens in HAERMONY Trial to Test HAE Gene Therapy

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by Steve Bryson, PhD |

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Enrollment is open for the open-label, Phase 1/2 HAERMONY trial to evaluate the safety and effectiveness of BMN 331, an investigational gene therapy for hereditary angioedema (HAE).

The trial’s sponsor, BioMarin Pharmaceutical, plans to recruit about 34 adults with type 1 or type 2 HAE at one site in Missouri. More information about enrollment and contact information can be found here.

HAE is a genetic disorder characterized by sudden and recurrent swelling in the hands, feet, face, upper airways, gastrointestinal tract, and genitals. Most cases are caused by inherited mutations in the SERPING1 gene, which carries instructions for making the C1-inhibitor (C1-INH) protein.

For people with type 1 HAE, these mutations impair C1-INH production, while the protein malfunctions for those with type 2 HAE. Not enough C1-INH activity results in abnormally high levels of a pro-inflammatory protein called bradykinin, which causes swelling attacks.

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BMN 331 is designed to provide a healthy copy of the SERPING1 gene to increase levels of C1-INH and reduce swelling attacks or keep them from occurring. The therapy is delivered to liver cells, where C1-INH is produced, by a harmless virus called AAV5 via a single infusion into the vein.

According to BioMarin, preclinical studies have demonstrated that BMN 331 can insert the SERPING1 gene into liver cells and restore C1-INH levels in the bloodstream.

The five-year HAERMONY trial (NCT05121376) will be a two-part study. Part A will assess the preliminary safety of single, escalating doses of BMN 331 and determine whether C1-INH increases in a dose-dependent manner. Part B will be a dose-expansion phase to find up to three safe doses that will sustain clinically meaningful C1-INH levels.

The trial’s primary goal is to assess the number of participants who develop side effects following the infusion. Secondary measures include evaluating HAE attacks’ number and severity, the annualized use of HAE medications, and the levels of antibodies targeting the C1-INH protein and the AAV5 viral delivery system.

Both males and females 18 and older with a genetically confirmed HAE diagnosis are eligible to participate. Patients must be receiving routine prophylactic (preventive) or on-demand therapy six months before enrolling for attacks that occur on average at least once a month.

Participants need to be trained to self-administer acute attack treatments and manage any attacks at home, be willing to abstain from consuming alcohol for at least one year after infusion, and use highly effective contraception, if applicable.

BMN 331 was granted an orphan drug designation by the U.S. Food and Drug Administration. This designation seeks to support the development of rare disease therapies by providing developers with incentives and benefits, including tax credits for clinical trials, exemption of certain fees, and a seven-year market exclusivity period upon approval.