ADVM-053 Receives Orphan Drug Designation for Treatment of Hereditary Angioedema


The FDA grants an orphan drug designation to a novel gene therapy candidate for the treatment of patients with hereditary angioedema.

The US Food and Drug Administration (FDA) has granted an orphan drug designation to Adverum Biotechnologies’ novel gene therapy candidate, ADVM-053, for the treatment of patients with hereditary angioedema.

“We are pleased to receive the orphan drug designation or ADVM-053 from the FDA,” Leone Patterson, interim president and chief executive officer of Adverum, said in a recent statement. “We are committed to developing effective treatments for patients living with HAE and the support from the FDA will be invaluable towards this goal.”

Hereditary angioedema type I and type II are caused by mutations in the SERPING1 gene, which plays a critical role in creating the C1 inhibitor protein that is essential for controlling inflammation. The mutations that cause hereditary angioedema type I result in reduced levels of C1 inhibitor in the blood and mutations that cause type II lead to the production of abnormal C1 inhibitors. When C1 inhibitors are not functioning as they should, copious amounts of bradykinin are created, which encourages inflammation by boosting the leakage of fluid through blood vessel walls into body tissues. The episodes of swelling commonly observed in patients with type I and type II are caused by an accumulation of those fluids in body tissues.

As such, the gene therapy was developed to serve as a potential single-administration treatment capable of preventing breakthrough attacks by sustaining the release of C1 esterase inhibitor protein to eliminate protein level variability.

"Our gene therapy ADVM-053 is unique in that it is designed to provide sustained release of C1EI with potentially a single intravenous injection," a representative from Adverum told Rare Disease Report®. "As a result, our therapy has the potential to significantly reduce treatment burden, eliminates peaks and troughs (or variability) of protein levels, and thus actually prevent breakthrough attacks."

The current standard of care for hereditary angioedema is prophylactic treatment, which can be burdensome and offers limited efficacy.

"C1EI (Cinryze) was the first treatment approved, but the intravenous infusions 2 to 3 times a week are burdensome. In addition, this therapy only offers limited efficacy, with attacks reduced by only 50%," he added. "More recently, Haegarda SC was launched in Q3 2017. In clinical trials, Haegarda SC demonstrated a 95% reduction of attacks vs. placebo when used as a prophylactic treatment; while effective, Haegarda still requires 2 to 3 subcutaneous injections a week and does not address peaks and troughs (or variability) of protein levels." As such, the gene therapy could be a potential gamechanger.

The treatment has shown success in preclinical studies, for which investigators evaluated a single intravenous dose of ADVM-053 to mice with HAE. For these studies, investigators found that the treatment effectively increased C1E1 protein expression above therapeutic levels and reduced vascular permeability.

The company plans to submit an investigational new drug application in the fourth quarter.

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