Pharvaris’ Deucrictibant Provides Rapid Relief for HAE in Phase 3 RAPIDe-3 Trial

Pharvaris announced that RAPIDe-3 met its primary endpoint, with deucrictibant relieving hereditary angioedema (HAE) symptoms in just under 90 minutes.1

The phase 3, placebo-controlled RAPIDe-3 trial evaluated deucrictibant, an oral immediate-release capsule (20 mg), for the on-demand treatment of HAE. Investigators evaluated this novel bradykinin B2 receptor antagonist in 134 participants aged ≥ 12 years from 24 countries on 6 continents.1

“Bradykinin B2 receptor antagonism is a proven and effective mechanism for treatment of bradykinin-mediated angioedema,” said lead investigator Marc A. Riedl, MD, professor of medicine and clinical director of the US Hereditary Angioedema Association (HAEA) Angioedema Center at the University of California, San Diego (UCSC), in a statement.1 “Injectable and oral on-demand therapies for HAE are available; however, unmet medical needs remain. The comprehensive and compelling outcomes of RAPIDe-3, specifically the fast treatment response and early complete symptom resolution, demonstrate the potential benefits of deucrictibant as an important on-demand treatment for people living with HAE.”

Riedl and colleagues assessed median time to treatment onset using the Patient Global Impression of Change (PGI-C); median time to substantial symptom relief using the PGI-C and Patient Global Impression of Severity (PGI-S); median time to complete symptom resolution using the PGI-S; and the percentage of attacks treated with a single capsule of deucrictibant. The sample included participants both on and off long-term prophylaxis; attacks of varying severity and across all body locations; and HAE subtypes, including type 1, type 2, and HAE with normal C1 inhibitor. This diverse population makes RAPIDe-3 highly representative and the first on-demand HAE study fully aligned with the Core Outcome Set recommended by the AURORA consensus.1

Compared to placebo, participants on deucrictibant responded to the treatment quicker— within 1.28 hours, on average, vs > 12 hours (P <.0001). Even minimal improvement, described as feeling “a little better,” counted as an onset of treatment response. Time to End of Progression 17.47 minutes for participants on deucrictibant vs 228.67 minutes for participants on placebo (P <.0001).1

Participants treated with deucrictibant also experienced a shorter median time to substantial symptom relief on the PGI-C—rated as “better”—compared with placebo (2.85 hours vs > 12 hours; P <.0001). Time to substantial symptom relief by PGI-S4 ≥ 1-level improvement was 2.41 hours vs > 12 hours, respectively.1

The median time to complete symptom resolution by PGI-S was significantly earlier with deucrictibant than placebo (11.95 hours vs > 24 hours; P <.0001). Additionally, deucrictibant reduced attack burden: within 12 hours, 83% of attacks resolved with a single deucrictibant immediate-release capsule, and 93.2% of attacks required no additional rescue medication.1

The study also showed that deucrictibant was well-tolerated with no treatment-related serious adverse events. The safety was consistent with completed and ongoing trials. Currently, investigators are conducting the ongoing RAPIDe-2 Part B, an open-label extension of deucrictibant for the on-demand treatment of HAE attacks.

“These clinically meaningful and statistically significant results demonstrate deucrictibant’s early-onset treatment response, fast symptom relief and resolution, and well-tolerated safety profile,” said Peng Lu, MD, PhD, chief medical officer of Pharvaris, in a statement.1 “This is an important step toward realizing deucrictibant’s potential to offer control of bradykinin-mediated angioedema attacks. With these data in hand, our team is working diligently to prepare for regulatory filings to enable access to this promising therapy.”

Pharvaris plans to submit a New Drug Application (NDA) for deucrictibant to the US Food & Drug Administration (FDA) in the first half of 2026. If approved, this would add yet another HAE treatment option for patients, building on the wave of HAE approvals seen in 2025, including garadacimab-gxii (Andembry), sebetralstat (Ekterly), and donidalorsen (Dawnzera), and setting the stage for the year ahead.2

References

1. Pharvaris Announces Positive Topline Data from RAPIDe-3 Pivotal Study Confirming Potential of Deucrictibant for On-Demand Treatment of HAE Attacks - Pharvaris N.V. Pharvaris N.V. Published 2025. Accessed December 5, 2025. https://ir.pharvaris.com/news-releases/news-release-details/pharvaris-announces-positive-topline-data-rapide-3-pivotal-study

2. Soteres D, Tachdjian R, Manning M, et al. Rare Disease, Rapid Progress: FDA's HAE Approvals in 2025 Signal Changing Course. HCPLive. December 3, 2025. https://www.hcplive.com/view/rare-disease-rapid-progress-fda-hae-approvals-in-2025-signal-changing-course. Accessed December 3, 2025.