Deucrictibant effective in 4 patients with acquired angioedema
Treatment prevents attacks in proof-of-concept trial
Deucrictibant, an experimental treatment for angioedema attacks, was well tolerated and effective in four patients with acquired angioedema due to C1-inhibitor deficiency (AAE-C1INH), according to a study.
The proof-of-concept trial found that the “deucrictibant extended-release tablet effectively prevented angioedema attacks in patients with AAE-C1INH, with no safety concerns,” the researchers wrote.
The study, “Long-term prophylactic treatment with deucrictibant for angioedema due to acquired C1-inhibitor deficiency,” was published in The Journal of Allergy and Clinical Immunology. It was funded by Pharvaris, the company developing deucrictibant.
AAE swelling attacks are driven by excessive production of bradykinin, a molecule that causes blood vessels to become more permeable and leak fluid into nearby tissues. This is caused by the lack of C1-inhibitor (C1-INH), a protein that normally regulates bradykinin production. AAE is commonly associated with other conditions, such as cancer or autoimmune diseases.
Deucrictibant is a small molecule that Pharvaris started developing as an on-demand and prophylactic (preventive) treatment for swelling attacks in people with hereditary angioedema, another bradykinin-mediated form of angioedema. It is designed to block the bradykinin B2 receptor, preventing bradykinin from interacting with its receptor and triggering swelling attacks. It’s available as immediate-release capsules (PHVS416) for on-demand treatment and extended-release tablets (PHVS719) for prophylactic therapy.
Promising results from earlier study
Deucrictibant showed promising efficacy as an on-demand and prophylactic treatment for swelling attacks in people with AAE in a recently published study reporting the results of a small, placebo-controlled trial (EudraCT number, 2021-000720-36).
In the latest study, the same team of researchers at Amsterdam University Medical Center reported on an open-label trial (EudraCT number, 2022-003168-25) that evaluated deucrictibant’s efficacy at preventing or treating swelling attacks in people with AAE-C1INH.
Four men with the condition, ranging in age from 39 to 69 and living with the disease for four to fourteen years, were enrolled. All had low C1-INH activity levels and were previously treated with rituximab and medications to prevent swelling attacks (danazol, C1-INH concentrates, and tranexamic acid).
All participants received 40 mg deucrictibant extended-release tablets, once daily, for up to 20 months. Three participants rolled over from the placebo-controlled trial, in which they had also received deucrictibant for eight weeks (about two months).
In the two months before the trial, all patients reported at least one AAE attack, with an average of 2.5 attacks per month. Three patients had no attacks during treatment. One had a mild abdominal attack two days after starting deucrictibant, and was successfully treated with icatibant (sold as Firazyr and generics).
All patients achieved complete angioedema control, demonstrated by a score of 16 in the Angioedema Control Test, and improved quality of life, according to the Angioedema Quality of Life questionnaire.
A total of 28 adverse events were reported, and most of them were mild. None was deemed related to the treatment or led to treatment discontinuation. Three severe adverse events were reported, including two cases of cancer.
Deucrictibant demonstrated consistently adequate exposure throughout the study, with a mean blood level of 49.2 nanograms per milliliter.
“This open-label study provides evidence that long-term prophylactic treatment with deucrictibant is effective, well tolerated, and safe in preventing angioedema attacks in patients with AAE-C1INH,” the researchers wrote.
The company plans to launch a pivotal Phase 3 trial by the end of the year to assess deucrictibant’s efficacy in treating and preventing swelling attacks in people with AAE.
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