Last year, the FDA placed a clinical hold on an Investigational New Drug (IND) application for deucrictibant for the on-demand and prophylactic treatment of individuals living with hereditary angioedema (HAE). While the FDA lifted the clinical hold on the IND for on-demand treatment, a clinical hold still remains for prophylactic treatment. However, reports Annalee Armstrong in Fierce Biotech, results from the Phase 2 CHAPTER-1 trial highlight the potential benefits of deucrictibant as a prophylaxis in this space.
Armstrong reports that 34 participants enrolled in the study; participants had either HAE types 1 or 2. Over a 12-week period, participants received either a placebo or one of two deucrictibant doses. Deucrictibant is described by Pharvaris, the drug’s developer, as:
a highly potent, specific, and orally bioavailable competitive antagonist of the bradykinin B2 receptor that utilizes the same mechanism as icatibant, the leading therapy for on-demand treatment of HAE. Pharvaris is developing this novel, oral, small molecule for on-demand and prophylactic treatment of HAE and other bradykinin-mediated diseases through formulations optimized for each setting.
The study found that a 40mg immediate-release capsule of deucrictibant reduced monthly HAE attacks by 84.5% during the course of the study. Additionally, HAE attacks were less severe and required less on-demand treatment. These findings suggest that deucrictibant could offer benefits for prophylactic care in HAE while reducing the overall treatment burden. Additionally, the results suggest that the therapy was both safe and relatively well-tolerated. While some adverse reactions occurred, these were mild in nature.
It is unclear what the plan is for deucrictibant as a prophylactic treatment moving forward. Pharvaris plans to submit study results to the FDA. The program will remain on a clinical hold until that point.
About Hereditary Angioedema (HAE)
Hereditary angioedema is a rare and potentially life-threatening genetic disorder that causes recurring attacks of unexplained and severe swelling (angioedema) beneath the skin. Its name gives insight into the condition: angio refers to blood vessels and edema refers to swelling caused by excess fluid in the bodily tissues. HAE results from a genetic defect on chromosome 11 that causes C1-inhibitor, a type of blood protein that regulates processes like inflammation and coagulation, to be defective. As a result, protein fragments called bradykinin accumulate, causing inflammation. While HAE affects both males and females, females may have more severe symptoms due to hormonal fluctuations. Hormonal fluctuations are one trigger for HAE attacks; stress, injury, surgery, or physical activity may also trigger attacks. However, the swelling does occasionally occur without a trigger.
People with HAE may experience swelling in the extremities, causing them to swell to 2x their normal size; facial swelling; intestinal swelling leading to abdominal discomfort, nausea, and vomiting; and throat swelling that may cause difficulty breathing. Without treatment, the U.S. Hereditary Angioedema Association suggests that laryngeal (throat) swelling can be fatal in 30% of cases.
If you have HAE and are newly diagnosed, consider checking out some of these supportive resources.
