Oral Deucrictibant Speeds Symptom Relief for Hereditary Angioedema Attacks

Oral deucrictibant produced significantly faster onset of symptom relief than placebo for hereditary angioedema (HAE) attacks in the phase 3 RAPIDe-3 trial, according to results published in The Lancet.

Deucrictibant is an oral bradykinin B2 receptor antagonist. The investigators noted that oral on-demand treatments allowing prompt administration and providing rapid, sustained relief remain scant for HAE, a rare bradykinin-mediated condition.

The double-blind, 2 × 2 crossover trial was conducted at 59 sites in 24 countries and enrolled adolescents (aged 12 to <18 years) and adults (aged 18-75 years) with HAE, including HAE with a normal C1 inhibitor associated with a documented genetic variant. Participants had at least 2 attacks in the 3 months before screening and experience effectively using conventional on-demand therapies. A total of 134 participants (10 adolescents and 124 adults; median age, 38 years; 57% female) were randomized 1:1 to treat 2 attacks, one with a 20mg oral deucrictibant immediate-release capsule and one with placebo, in either order.

The primary endpoint was time to onset of symptom relief, defined as a Patient Global Impression of Change rating of at least “a little better.” Among 88 participants with paired treated attacks included in the primary efficacy analysis, median time to onset of symptom relief was 1.28 hours (95% CI, 1.05-1.52) with deucrictibant vs more than 12 hours with placebo (P < 0.0001).

Fatigue was the only adverse event reported more than once within 3 days of treatment, occurring in 2 participants, and 1 event was deemed unrelated to treatment. Across the study, no treatment-related adverse events were assessed as severe or serious, and no adverse events led to treatment discontinuation. The investigators concluded that the results support deucrictibant as potentially the first orally administered bradykinin B2 receptor antagonist for treating attacks of bradykinin-mediated angioedema, including HAE. The trial was funded by Pharvaris.

Source: Riedl MA, Li PH, Adatia A, et al. Oral deucrictibant for on-demand treatment of hereditary angioedema attacks: a phase 3, multicentre, randomised, double-blind, placebo-controlled crossover trial. Lancet. Published online October 8, 2026. doi:10.1016/S0140-6736(26)01296-1