Oral Deucrictibant Reduces HAE Attack Severity in 4 Hours During Phase 2 RAPIDe-1

In the phase 2 RAPIDe-1 trial, oral deucrictibant significantly reduced the severity of hereditary angioedema (HAE) attacks in 4 hours compared with the placebo.1

“…these results support continued investigation of antagonism of the bradykinin B2 receptor with an orally available agent as a potentially effective approach, with a safety profile similar to placebo, for on-demand treatment,” wrote study investigators Marc A. Riedl, from the University of California San Diego; Emel Aygören-Pürsün, MD, from Goethe University Frankfurt; and colleagues.1

Before the publication of this phase 2 data, Pharvaris announced that oral deucrictibant 20 mg met its primary endpoint in the placebo-controlled phase 3 trial, showing symptom relief in under 90 minutes.2 The mean time to symptom relief with oral deucrictibant was within 1.28 hours, compared to > 12 hours with a placebo.

In the recently published phase 2 randomized, double-blind, placebo-controlled, crossover study, adults with HAE type 1 or 2 experienced clinically meaningful improvements in symptom burden and time to relief when treated with deucrictibant at doses of 20 mg or 30 mg.1 Among 62 patients included in the modified intention-to-treat analysis, deucrictibant demonstrated significant reductions in the composite visual analog scale (VAS-3) score at 4 hours compared with the placebo. Least squares mean differences were −15.02 (95% CI, −20.22 to −9.81; P <.0001) for 20 mg and −16.28 (95% CI, −21.27 to −11.29; P <.0001) for 30 mg. A 10 mg dose showed similar directional effects but was evaluated descriptively.1

Clinical benefits extended to key secondary endpoints. Median time to onset of symptom relief, defined as a ≥ 30% reduction in VAS-3, was 2.7 hours for 20 mg and 2.5 hours for 30 mg, compared with 8.0 hours for placebo. Time to a ≥ 50% reduction in symptoms and to near-complete or complete resolution was also significantly shorter with deucrictibant. Within 24 hours, 71% of attacks treated with 20 mg and 74% with 30 mg achieved near-complete or complete resolution without rescue medication, compared with 16% of placebo-treated attacks.1

Use of rescue therapy was lower with deucrictibant. Within 24 hours, 11% and 13% of attacks treated with 20 mg and 30 mg, respectively, required rescue medication versus 73% with placebo (odds ratios 0.05–0.06; P <.0001). These findings suggest both rapid onset and durability of response.1

The study reported no grade 3 or higher treatment-emergent adverse events. Most adverse events were mild to moderate and considered unrelated to the study drug. In part 2 of the trial, no single adverse event occurred in ≥ 2 patients within any treatment group. Oral administration avoids injection-site reactions commonly associated with subcutaneous bradykinin B2 receptor antagonists.

Pharmacokinetic data showed plasma concentrations exceeding the estimated threshold for 85% maximal response within 15 to 30 minutes of dosing, aligning with observed early clinical effects. Symptom improvement was detectable within the first hour across multiple outcome measures.1

Current on-demand HAE therapies, including C1 esterase inhibitors, icatibant, and ecallantide, require intravenous or subcutaneous administration, which can delay treatment initiation. Although the recently approved plasma kallikrein inhibitor sebetralstat offers an oral option, deucrictibant represents the first oral bradykinin B2 receptor antagonist evaluated in a randomized controlled trial for acute HAE treatment, according to the investigators.

The team noted several limitations, including the exclusion of laryngeal attacks and those with vomiting, limiting generalizability to greater risk presentations. The study population was predominantly White, and the attack location was not randomized, which may influence response patterns.

Ongoing phase 3 studies are expected to further define the role of deucrictibant in both on-demand and prophylactic HAE treatment strategies. Investigators noted that the phase 3 trial will include a broader geographical and racial representation.

“Together with the results of the CHAPTER-1 trial (NCT05047185) for prophylaxis of angioedema attacks conducted in parallel, outcomes of RAPIDe-1 provide the first clinical evidence, to our knowledge, that antagonism of the bradykinin B2 receptor with deucrictibant could be effective and well tolerated and that deucrictibant might be the first oral therapy for both prevention and treatment of bradykinin-mediated angioedema attacks,” investigators concluded.1

References

1. Maurer M, Stobiecki M, Valerieva A, et al. Oral deucrictibant for on-demand treatment of hereditary angioedema attacks (RAPIDe-1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Haematol. 2026;13(4):e200-e214. doi:10.1016/S2352-3026(25)00341-2

2. Derman C. Pharvaris’ Deucrictibant Provides Rapid Relief for HAE in Phase 3 RAPIDe-3 Trial. HCPLive. Published December 8, 2025. Accessed on April 29, 2026. https://www.hcplive.com/view/pharvaris-deucrictibant-provides-rapid-relief-hae-phase-3-rapide-3-trial